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PubMed2001

Leaching of toluene-neoprene adhesive wastes.

This work consists of the study of the extraction of solvent (toluene) from a polymeric (neoprene) substrate during a leaching process. Total organic carbon (TOC) is the main contaminant parameter in the leaching of these systems due to the solution of the toluene and the dispersion of the polymer. The toxicity of the extracts was measured with a Microtox equipment, using Photobacteria phosphoreum, deducing that the toxicity of the extracts is low due to the low solubility of toluene but that the toxicity of toluene is high. On the basis of the experimental results, the amount of toluene diffused vs time in plane sheet systems was studied. A kinetic model has been developed considering two stages: In the first stage, the toluene diffuses into the system across the neoprene chains at a constant rate, not depending on the initial toluene concentration. This fact is explained by considering that there is a constant difference of the toluene concentration between the interface with the water and the inner part of the sample. In the second stage, the dispersion of the polymer with the corresponding amount of toluene takes place. The diffusion of toluene in the leaching process is compared and analyzed considering the diffusion of toluene in a desorption process in air so that the difference of toluene concentration between the interface and the interior can be estimated. A mathematical model is also proposed for considering the leaching process in other operating conditions.

Adhesives↗
PubMed2003

Use of a site-specific recombination-based biosensor for detecting bioavailable toluene and related compounds on roots.

We constructed and characterized a plasmid-based genetic system that reports the expression of a toluene-responsive promoter (PtbuA1) by effecting an irreversible, heritable change in the biosensor cell. Expression of the reporter gene gfp is strongly repressed in the absence of expression from the PtbuA1 promoter, and high level gfp expression in the original cell and its progeny is mediated by the site-specific recombination machinery of bacteriophage P22 to initiate removal of a repressor cassette. The reporter plasmid pTolLHB was functional in two soil saprophytes, Pseudomonas fluorescens A506 and Enterobacter cloacae JL1157, with the efficiency and sensitivity to low toluene concentrations being optimal in P. fluorescens A506. In culture, 80-100% of the A506 (pTolLHB) population expressed gfp following exposure to 0.2 micro m toluene for one to three hours. Compared to the response of A506 containing a plasmid-borne PtbuA1-gfp fusion, the recombination-based biosensor was more sensitive at detecting low toluene and trichloroethylene concentrations. An A506 (pTolLHB) inoculum, which had a background of 2.5% of the cells expressing gfp, was introduced onto barley roots in soil microcosms. If toluene was introduced into the microcosms, after 24 h, 72% of the A506 (pTolLHB) cells recovered from roots expressed gfp, indicating bioavailable toluene to rhizosphere bacteria. When toluene was not introduced, 16.5% of the A506 (pTolLHB) cells recovered from the roots expressed gfp, indicating that natural inducers of the PtbuA1 promoter were present in the barley rhizosphere. When introduced into rhizotrons containing barley plants and toluene vapours, the biosensor allowed localization of the availability of toluene along the seminal roots. In rhizotrons that were not exposed to toluene vapours, the biosensor exhibited high PtbuA1-promoter activity in distinct regions along the seminal roots, indicating spatial heterogeneity plant- or rhizosphere microbial community-derived inducers of the PtbuA1 promoter. This recombination-based toluene biosensor thus was useful in identifying bacterial exposure to transient or low levels of toluene, or related compounds, directly in the environment.

Bacteria↗
PubMed2003

Occupational toluene exposure and auditory function: results from a follow-up study.

The ototoxicity of occupational exposure to toluene below 50 p.p.m. was investigated in a longitudinal study over 5 yr with four repeated examinations starting with 333 male workers from rotogravure printing plants. Past lifetime weighted average exposures (LWAE) to toluene and noise were determined from individual work histories; recent individual exposures were measured 10 times during the study (toluene, active sampling; noise, stationary measurements). The auditory thresholds were measured with pure tone audiometry. The mean LWAE exposures to toluene and noise were 45 +/- 17 p.p.m. plus 82 +/- 7 dB(A) for printers (high toluene intensity) and 10 +/- 7 p.p.m. plus 82 +/- 4 dB(A) for end-processors (low toluene intensity). The mean current exposures to toluene and noise during the study were 26 +/- 20 p.p.m. plus 81 +/- 4 dB(A) for printers and 3 +/- 3 p.p.m. plus 82 +/- 4 dB(A) for end-processors. Repeated measurement analyses (grouping factors: toluene intensity, exposure duration and noise intensity) and logistic regressions did not reveal significant effects of toluene intensity, of exposure duration and of interactions between toluene intensity and noise intensity. The stratification dependent on noise intensity itself [79 +/- 3 versus 84 +/- 1 dB(A)] was significantly associated with the auditory thresholds. Regarding the missing toluene effects, it was concluded that the threshold level for developing a hearing loss as a result of occupational toluene exposure might be above the actual limit of 50 p.p.m.

Follow-Up Studies↗
PubMed1990

Effect of toluene on ethanol preference in rats.

The effect of toluene on the preference of ethanol was studied in rats. Toluene was administered orally by stomac tube in doses of 200, 400 or 800 mg/kg daily for 5 weeks or by inhalation at a concentration of 2000 p.p.m. 6 or 8 hr daily for 5 or 6 days per week for 2 weeks in rats of different age. During toluene inhalation exposure the rats had access to either tap water or ethanol-containing water (6 or 10%). After the exposure and during oral administration the rats had access to both ethanol-free and ethanol-containing water. Toluene inhibited the body weight gain in the highest oral dose group and in rats exposed to toluene and forced to drink ethanol in the inhalation experiments. In these experiments, the intake of fluid was reduced in the exposure period in rats forced to drink ethanol-containing water and further reduced in rats exposed to both ethanol and toluene. Exposure to toluene alone increased the fluid consumption. The preference of ethanol defined as consumed ethanol-containing water in per cent of the total water intake was not influenced by oral administration of toluene. It was, however, reduced by toluene given by inhalation to rats forced to drink ethanol-containing water during the exposure period. Toluene exposure alone or forced ethanol intake alone caused in these experiments a short-lasting reduction of the ethanol preference. It is concluded that toluene decreases the preference of ethanol in rats forced to drink ethanol during exposure to toluene.

Administration, Inhalation↗
PubMed1992

Microbial degradation of toluene under sulfate-reducing conditions and the influence of iron on the process.

Toluene degradation occurred concomitantly with sulfate reduction in anaerobic microcosms inoculated with contaminated subsurface soil from an aviation fuel storage facility near the Patuxent River (Md.). Similar results were obtained for enrichment cultures in which toluene was the sole carbon source. Several lines of evidence suggest that toluene degradation was directly coupled to sulfate reduction in Patuxent River microcosms and enrichment cultures: (i) the two processes were synchronous and highly correlated, (ii) the observed stoichiometric ratios of moles of sulfate consumed per mole of toluene consumed were consistent with the theoretical ratio for the oxidation of toluene to CO2 coupled with the reduction of sulfate to hydrogen sulfide, and (iii) toluene degradation ceased when sulfate was depleted, and conversely, sulfate reduction ceased when toluene was depleted. Mineralization of toluene was confirmed in experiments with [ring-U-14C]toluene. The addition of millimolar concentrations of amorphous Fe(OH)3 to Patuxent River microcosms and enrichment cultures either greatly facilitated the onset of toluene degradation or accelerated the rate once degradation had begun. In iron-amended microcosms and enrichment cultures, ferric iron reduction proceeded concurrently with toluene degradation and sulfate reduction. Stoichiometric data and other observations indicate that ferric iron reduction was not directly coupled to toluene oxidation but was a secondary, presumably abiotic, reaction between ferric iron and biogenic hydrogen sulfide.

Biodegradation, Environmental↗
PubMed1998

Efflux pumps involved in toluene tolerance in Pseudomonas putida DOT-T1E.

The basic mechanisms underlying solvent tolerance in Pseudomonas putida DOT-T1E are efflux pumps that remove the solvent from bacterial cell membranes. The solvent-tolerant P. putida DOT-T1E grows in the presence of high concentrations (e.g., 1% [vol/vol]) of toluene and octanol. Growth of P. putida DOT-T1E cells in LB in the presence of toluene supplied via the gas phase has a clear effect on cell survival: the sudden addition of 0.3% (vol/vol) toluene to P. putida DOT-T1E pregrown with toluene in the gas phase resulted in survival of almost 100% of the initial cell number, whereas only 0.01% of cells pregrown in the absence of toluene tolerated exposure to this aromatic hydrocarbon. One class of toluene-sensitive octanol-tolerant mutant was isolated after Tn5-'phoA mutagenesis of wild-type P. putida DOT-T1E cells. The mutant, called P. putida DOT-T1E-18, was extremely sensitive to 0.3% (vol/vol) toluene added when cells were pregrown in the absence of toluene, whereas pregrowth on toluene supplied via the gas phase resulted in survival of about 0.0001% of the initial number. Solvent exclusion was tested with 1,2,4-[14C]trichlorobenzene. The levels of radiochemical accumulated in wild-type cells grown in the absence and in the presence of toluene were not significantly different. In contrast, the mutant was unable to remove 1,2,4-[14C]trichlorobenzene from the cell membranes when grown on Luria-Bertani (LB) medium but was able to remove the aromatic compound when pregrown on LB medium with toluene supplied via the gas phase. The amount of 14C-labeled substrate in whole cells increased in competition assays in which toluene-and xylenes were the unlabeled competitors, whereas this was not the case when benzene was the competitor. This finding suggests that the exclusion system works specifically with certain aromatic substrates. The mutation in P. putida DOT-T1E-18 was cloned, and the knockedout gene was sequenced and found to be homologous to the drug exclusion gene mexB, which belongs to the efflux pump family of the resistant nodulator division type.

Amino Acid Sequence↗
PubMed1992

Influence of various mixtures of inhaled toluene and xylene on the biological monitoring of exposure to these solvents in rats.

The present study was undertaken to describe the influence of simultaneous exposure by inhalation to toluene and xylene on some aspects of their respective metabolic disposition. Adult male rats were exposed acutely (5 h) to 75, 150, and 225 ppm of toluene or xylene and to various mixtures of these solvents: toluene (75 ppm) and xylene (225 ppm), toluene (150 ppm) and xylene (150 ppm), toluene (225 ppm) and xylene (75 ppm). Compared with single exposure, simultaneous exposure resulted in lower amounts of excreted hippuric acid (20-30%) and methylhippuric acids (4-40%) in urine over a period of 24 h, even though significant differences were seen only with the toluene (150 ppm) and xylene (150 ppm) combination. In addition, increased concentrations of solvents in blood (toluene, 230%; xylene, 500%) and in brain (toluene, 230%; xylene, 320%) were found during the immediate post-exposure period. Simultaneous exposure also enhanced the pulmonary elimination of both solvents (toluene, 190-240%; xylene, 340-650%). Influence of repeated simultaneous exposure (9 days) was investigated for the toluene (150 ppm) and xylene (150 ppm) combination and the results compared with those of repeated exposure to each solvent administered singly. Under these conditions, repeated simultaneous exposure decreased the excretion of urinary metabolites, but only after the first exposure. On the other hand, simultaneous exposure resulted in significantly higher concentrations of toluene (210%) and xylene (240%) in blood throughout the entire 9-day exposure period. These results strongly suggest mutual metabolic interactions (inhibition) between toluene and xylene that affect the metabolic disposition of both solvents and ultimately the biological monitoring of data of exposure to a combination of solvents in rats.

Administration, Inhalation↗
PubMed1990

An ultrastructural evaluation of toluene toxicity using cultured mammalian cells.

Animal cells were cultured in media containing toluene and then examined by electron microscopy to determine changes in subcellular architecture. Cellular viability and cloning studies indicated toluene toxicity at concentrations of 50-500 ppm. At all dosage levels, toluene accelerated cell death compared to comparable control cells that had not been exposed to toluene. However, media composition and, particularly, the presence or absence of fetal bovine serum (FBS), markedly affected toluene toxicity. In media without FBS reversible changes in filopodia and cell shape were identified after 15 min of exposure to as little as 50 ppm toluene, and cell death occurred within 5 min at concentrations of 500 ppm toluene. In media with FBS, no filopodial changes were observed at 50 ppm toluene, and cell death, although accelerated, was clearly evident only after 24-48 h of exposure to 200-500 ppm toluene. Except for the cell-surface changes, chronic toluene exposures (50-100 ppm without FBS or 200-500 ppm with FBS in the growth medium) produced no unusual intracellular changes until 24-48 h of toluene exposure. With toluene exposures of 24 h or longer, cellular changes included condensation of heterochromatin in nuclei, formation of bulbous protuberances at the cell surface, loss of polyribosomes (but not ribosomes) and, ultimately, degeneration of organelles. These late changes were irreversible and the prelude to cell death.

Animals↗
PubMedDate not supplied

Effects of ethanol on toluene metabolism in man.

The aim of this paper was to study the possible causes for metabolism changes due to ethanol and solvents interactions. In literature the effects of interaction between some solvents (toluene, xilene, TCE, etc.) and ethanol in acute experimental exposure are well known: the ingestion of a moderate amount of ethanol (0.8 gr/Kg) before inhalatory exposure to solvents causes the hematic levels of the solvent itself to increase and the urinary excretion of the main metabolites to decrease. In our study we have analyzed the possible effects of exposure to toluene vapours on elimination of toluene itself in urine, which is a useful biological index of occupational exposure to toluene. 5 healthy volunteers were exposed to toluene vapours (100 mg/m3 for 4 hours) with and without simultaneous ethanol consumption (0.5 g ethanol/Kg body weight) in an exposure chamber. The ethanol was ingested two minutes before entering the chamber and two hours after beginning of exposure in order to reach ethanol and toluene maximal concentrations in blood simultaneously. The blood and urine were collected at the beginning and at the end of exposure in order to measure toluene and ethanol. The analyses were performed by means of a Gas Chromatograph (GC) Hewlett-Packard 5880 A connected with a Mass Selective Detector (MSD). The obtained results show that ethanol causes a decrease in toluene metabolism: in fact, with constant environmental exposure, toluene concentration at the end of exposure increases in blood from 156 micrograms/L to 285 micrograms/L (+84%) in presence of ethanol; the same happens to the amount of toluene eliminated in urine (+45% in presence of ethanol), while the metabolized amount of toluene (hippuric acid in urine) was lower in presence of ethanol (1492 mg/g creatinine in comparison with 2251 mg/g creatinine; 37%). These results show that a moderate amount of ethanol changes toluene metabolism: this phenomenon may be an important source of error in the biological monitoring of solvent exposure.

Administration, Inhalation↗
PubMed2001

Multicenter field trial on possible health effects of toluene. II. Cross-sectional evaluation of acute low-level exposure.

Data on possible acute effects of today's relevant low-level exposure to toluene are contradictory, and information on possible effects of exposure under occupational conditions is largely lacking. In a controlled, multi-center, blinded field trial, effects possibly associated with acute toluene exposure were evaluated in workers of 12 German rotogravure factories. Medical examinations (inquiries on subjective symptoms, and standard tests of psycho-physiological and psycho-motor functions) were performed on almost 1500 volunteers, of whom 1290 were toluene-exposed (1178 men and 112 women), and about 200 participants served as references (157 men and 37 women), but the main aim of the trial was to reveal dose-response relationships. All volunteers were of the morning work-shift (6 h exposure). Both individual ambient air concentrations (time-weighted average) during the work-shift, as well as blood toluene concentrations after the work-shift were measured. Therefore, the medical data could for the first time be correlated with the actual individual body burden (blood toluene level) at the time of testing. In order to largely exclude confounding by chronic toluene exposure, kinetic measurements as well as the psycho-physiological and psycho-motoric tests were performed before and after the work-shift. Except for minor statistical deviations, neither convincing dose-dependent acute effects could be demonstrated with regression analyses in male volunteers at the exposure levels evaluated, nor were significant differences found when applying group statistics (highly toluene-exposed group versus volunteers with negligible exposure). Due to the rather large number of participants, the predictive power of the study is high, especially when compared with previous publications. In two psycho-physiological tests, a few more female volunteers with quite low toluene body burdens (<340 microg/l blood) showed relatively low scores when compared with participants of the reference group. Although evidence for a medical relevance is meager, the small numbers of participants, in both the exposure and the reference groups, hamper a reliable interpretation of the results concerning exposure levels above 85 microg toluene/l blood, and it is difficult to take confounding factors adequately into account. For the end points evaluated and under occupational conditions, neither blood toluene levels of 850 to 1700 microg/l (in the highest exposure group [EXPO-IV] with 56 participants), as measured 1/2 (+/-1/2) h after the work-shift, nor ambient air concentrations (time-weighted average over 6 h) between 50 and 100 ppm (188-375 mg/m(3)) were convincingly associated with alterations in psycho-physiological and psycho-motoric performances or increased the frequency of subjective complaints in male volunteers. For higher dose ranges of toluene exposure (i.e. >1700 microg toluene/l blood [or >100 ppm in ambient air]), our data set is too small for far reaching conclusions. Our data are insufficient for conclusions on a possibly higher susceptibility to toluene of some female workers. Results of kinetic studies and possible effects of long-term exposure are discussed in two accompanying publications (Neubert et al., 2001; Gericke et al., 2001).

Acute Disease↗
PubMed1988

Toluene-induced alterations in rat synaptosomal membrane composition and function.

Toluene is a widely used organic solvent that can produce acute central nervous system (CNS) effects. Since toluene reaches relatively high concentrations in the CNS and is extremely lipophilic, we investigated its effects on rat brain membrane composition and function. Toluene (1 g/kg, lh) did not alter total brain microsomal phospholipid (PL) or cholesterol (CL) content. However, synaptosomal PL was decreased (24%), while synaptosomal CL was unaltered. The PL/CL ratio, an indirect index of membrane fluidity, did not change, suggesting that toluene did not affect membrane fluidity. Fluorescence polarization studies employing 1,6-diphenyl-1,3,5-hexatriene (DPH) showed that toluene did not alter synaptosomal membrane fluidity after administration in vivo (1 g/kg) or in vitro (0.5 to 5.0 mM). Dose-response and time-course studies showed that toluene maximally decreased synaptosomal PL after 1 g/kg, 1 h. The dose-response and time-course studies also showed that the toluene-induced decreases in PL were a result of specific decreases in phosphatidylethanolamine (PE). Since PE was decreased, we assessed whether toluene altered synaptosomal membrane function by investigating phospholipid methylation, a reaction which uses PE as its initial substrate. Toluene decreased the incorporation of methyl groups into lipid when [3H]-methionine was used as the methyl donor, but did not affect methylation when [3H]-adenosylmethionine was the methyl donor. These data suggest that toluene-induced specific decreases in synaptosomal PE and inhibition of phospholipid methylation may alter normal synaptic function and play a critical role in the mechanism(s) of action of toluene's CNS effects.

Animals↗
PubMed2000

Low-level toluene disrupts auditory function in guinea pigs.

Toluene appears to have adverse effects on the human auditory system, but it is difficult to estimate its potency since it is commonly present in the workplace in combination with noise exposure; workplace noise exposures are often highly variable. Studies designed to assess toluene ototoxicity specifically have been limited to high-dose studies in a single laboratory animal model, the rat. Here permanent hearing loss has been observed at concentrations of 1000 ppm toluene and greater after inhalation exposure for 5 days, 6 h/day. The OSHA threshold limit value for toluene is only 100 ppm. The current study focuses on the onset of toluene ototoxicity acutely in the guinea pig and in adducing a mechanism of effect. In this study, evidence is presented for the impairment of auditory function by toluene in the guinea pig, at a concentration substantially lower than that used for studying permanent impairment in the rat. The impaired function was correlated with reduced energy metabolism in outer hair cells. Assessment of auditory function was made using distortion product otoacoustic emissions (DPOAE) with subsequent measurement of succinate dehydrogenase (SDH) staining density in hair cells using surface preparations. Temporary disruption of auditory function in guinea pigs is seen in subjects exposed to 250, 500, and 1000 ppm toluene for 8 h/day, 5 day/week for 1 and 4 weeks. Concentrations as low as 250 ppm toluene were able to disrupt auditory function acutely in the guinea pig, and 500 and 1000 ppm toluene produced greater acute dysfunction. SDH staining suggests that reduced enzyme activity in the midfrequency region of the cochlea occurs acutely following toluene exposure. Although the auditory dysfunction progressed between 1 and 4 weeks of exposure, a permanent loss did not develop for these subjects and hair cell death was not seen. The current study identifies early evidence of auditory system impairment in the guinea pig at low toluene concentration and evidence for impairment of energy production in hair cells. While even a transient auditory impairment has implications for workplace safety, additional study on the transition from such acute effects to permanent impairment is essential.

Animals↗
PubMed1988

Toluene in venous blood during and after work in rotogravure printing.

Toluene exposure was studied in 62 male rotogravure printers, employed in three plants. The exposure level as measured by personal sampling during a week ranged from 8 to 1080 mg/m3 (median 96). The concentration of toluene in venous blood sampled directly after work correlated significantly with the time-weighted average (TWA) for toluene in air during the preceding workshift (n = 57, Spearman's r = 0.84, P less than 0.00001). The post-shift toluene level in venous blood is usable for biological monitoring of exposure. An air level of 100 mg/m3 corresponds to an average blood toluene level of 2.9 mumol/l; an air level of 300 mg/m3 to 8.2 mumol/l. The elimination of toluene is slow. Thus, toluene was detected in most Monday pre-shift blood samples and the levels increased statistically significantly during the work week (median 0.21 versus 0.42 mumol/l, P less than 0.0001). The toluene level in venous blood sampled directly before work on Thursday/Friday was found to be a function of the estimated mean exposure during the work week. In a multiple linear regression analysis, the mean exposure during the week was a good predictor for the concentration of toluene in venous blood before work at the end of the week (n = 52, r = 0.71). Thus, pre-shift blood values at the end of the week can be used as a biological index for the weekly exposure, when the variation of the ambient toluene concentration is known. The slow decrease of toluene in venous blood was followed in six workers for two weeks after cessation of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Toluene-induced oxidative stress in several brain regions and other organs.

The in vivo dose-response relationship between toluene and reactive oxygen species (ROS) formation in rat brain, liver, kidney, and lung, and the time-course of these effects has been characterized. The rate of oxygen radical formation was measured using the probe 2',7'-dichlorofluorescin diacetate. In vivo exposure to various doses of toluene (0.5, 1.0, and 1.5 g/kg ip) elicited a dose-dependent elevation of ROS generation within crude mitochondrial fractions obtained from rat lung and kidney, and within crude synaptosomal fractions from cerebellum. ROS formation in crude mitochondrial fractions from liver, and crude synaptosomal fractions from striatum and hippocampus, reached a maximum value at relatively low doses of toluene. Of the brain regions, the hippocampus had the highest induced levels of ROS. In vivo exposure to a single dose of toluene (1.5 g/kg ip), revealed that toluene-induced ROS reached a peak within 2 h, which correlated directly with measured toluene blood levels. This elevated oxidative activity was maintained throughout the next 24 h, even though blood values of toluene decreased to negligible amounts. These results demonstrate that exposure to toluene results in broad systemic elevation in the normal rate of oxygen radical generation, with such effects persisting in the tissues despite a rapid decline in toluene blood levels. Acute exposure to toluene may lead to extended ROS-related changes, and this may account for some of the clinical observations made in chronic toluene abusers.

Animals↗
PubMed1993

Free radical induction in the brain and liver by products of toluene catabolism.

Toluene and its metabolites have been studied with respect to their reactive oxygen species-enhancing potential in isolated systems and in vivo. The induction of reactive oxygen species (ROS) production was assayed using the probe 2',7'-dichlorodihydrofluorescin diacetate (DCFH-DA). Intraperitoneal injection of toluene, benzyl alcohol or benzaldehyde caused a significant elevation in the rate of ROS formation within hepatic mitochondrial fractions (P2). In the brain, only toluene induced ROS formation, while benzyl alcohol and benzaldehyde did not have any effect. Glutathione (GSH) levels were depressed in liver and brain regions from toluene-treated rats. However, no such depression was evident in brains treated with toluene metabolites. P2 fractions from phenobarbital-pretreated rats exhibited a heightened ROS response when challenged with toluene, in vitro. Pretreatment of rats in vivo with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, or sodium cyanamide, an aldehyde dehydrogenase inhibitor, prior to exposure to toluene, caused a significant decrease and increase, respectively, in toluene-stimulated rates of ROS generation in the CNS and liver. Electron spin resonance spectroscopy, employing the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), was conducted. Incubation of the spin trap with P2 fractions and toluene or benzaldehyde elicited a spectrum corresponding to the hydroxyl radical. Incubation of benzaldehyde with aldehyde dehydrogenase produced a strong signal that was blocked completely by superoxide dismutase and inhibited partially by catalase, suggesting the presence of superoxide radicals and the involvement of the iron-catalyzed Haber-Weiss reaction leading to the production of hydroxyl radicals. Thus, ROS generation during toluene catabolism may occur at two steps: cytochrome P450 oxidation and aldehyde dehydrogenase oxidation. In addition, GSH may play an important role in protection against the induction of ROS generation in the CNS and liver following exposure to toluene.

Aldehyde Dehydrogenase↗
PubMed2005

Alterations in glutamatergic and gabaergic ion channel activity in hippocampal neurons following exposure to the abused inhalant toluene.

Toluene, a representative member of the large class of abused inhalants, decreases neuronal activity and depresses behavior in both animals and humans. The sites of action of toluene are not completely known but recent studies suggest that ion channels that regulate neuronal excitability may be particularly sensitive. Previous studies with recombinant receptors showed that toluene decreases currents carried by N-methyl-D-aspartate (NMDA)-glutamate receptors without affecting those gated by non-NMDA receptors. In addition, toluene increases currents generated by GABA and glycine receptors. In the present study, primary cultures of rat hippocampal neurons were used to investigate the effects of acute and chronic toluene exposure on native excitatory and inhibitory ligand-gated ion channels. Toluene dose-dependently inhibited NMDA-mediated currents (IC50 1.5 mM) but had no effect on responses evoked by the non-NMDA agonist kainic acid. Prolonged treatment of neurons with toluene (1 mM; 4 days) increased whole-cell responses to exogenously applied NMDA, reduced those evoked by GABA but did not alter responses generated by kainic acid. Immunoblot analysis revealed that prolonged toluene exposure increased levels of NR2A and NR2B NMDA receptor subunits with no change in NR1. Immunohistochemical analysis with confocal imaging showed that toluene-treated neurons had significant increases in the density of NR1 subunits as compared with control neurons. Toluene exposure increased the amplitude of synaptic NMDA currents and decreased those activated by GABA. The results from this study suggest that toluene induces compensatory responses in the functional expression of ion channels that regulate neuronal excitability.

Amino Acid Transport System X-AG↗
PubMed2006

Cardiovascular effects of oral toluene exposure in the rat monitored by radiotelemetry.

Toluene is a hazardous air pollutant that can be toxic to the nervous and cardiovascular systems. The cardiotoxicity data for toluene come from acute studies in anesthetized animals and from clinical observations made on toluene abusers and there is little known on the response of the cardiovascular and other autonomic processes to graded doses of toluene. This study assessed the effects of toluene (0.4, 0.8, and 1.2 g/kg; gavage) on heart rate (HR), blood pressure, core temperature (Tc), and motor activity (MA) in unrestrained, male Long-Evans rats monitored by telemetry. Toluene doses of 0.8 and 1.2 g/kg elicited significant elevations in HR, characterized by a transient 100 beats/min increase in HR lasting 1 h followed with a steady state tachycardia lasting >6 h. Overall, HR increased by 25 and 50 beats/min in the 0.8 and 1.2 g/kg groups, respectively. MA increased markedly in the 0.8 and 1.2 g/kg groups but the tachycardia persisted in spite of recovery of MA in the 0.8 g/kg group. There was a small (<0.5 degrees C) increase in Tc above controls in rats dosed with 0.8 g/kg toluene, whereas 1.2 g/kg toluene elicited a transient reduction in Tc followed by a small elevation lasting several hours. In a second study, rats were implanted with transmitters to monitor blood pressure (BP), and were administered with toluene as in the first study. HR, Tc, and MA were also monitored. The tachycardic effects of toluene at 0.8 and 1.2 g/kg were associated with a rise in blood pressure. Doses of 0.8 and 1.2 g/kg elicited a mean BP elevation of 6 and 16 mm Hg, respectively, for 7-hour post-dosing. The biphasic tachycardia to toluene suggests multiple sites for eliciting the cardiotoxic effects of this toxicant.

Administration, Oral↗
PubMed2000

Effect of toluene inhalation on astrocytes and neurotrophic factor in rat brain.

Toluene, an abused substance in Japan, is a neurotoxic chemical that has been shown to have neurobehavioral and electrophysiological effects. In previous work, both acute and chronic effects of toluene on cells have been studied extensively. However, although glial cells are thought to play an important role in the survival of neurons in the brain, the effect of toluene on glial cell function has not yet been characterized. To elucidate this, the effect of toluene inhalation on astrocytes in rat brain was examined. Toluene exposure (1500 ppm for 4 h on 4-10 days) augmented glial fibrillary acidic protein (GFAP) immunoreactivity, particularly in the hippocampus and cerebellum. Quantitative analysis showed that toluene inhalation markedly enhanced GFAP expression in the hippocampus and cerebellum. In both regions, proliferating cell nuclear antigen (PCNA) showed no obvious changes, but glutamine synthetase (GS)-immunoreactive cells were markedly increased by toluene exposure. Thus, the elevation of GFAP expression was induced by astrocyte activation rather than by cell proliferation. If toluene exposure activates astrocytes, astrocytes may play a role in the neurophysiological changes observed in toluene intoxication. A neurotrophic factor, basic fibroblast growth factor (b-FGF) was observed immunohistochemically in the capillary vessel walls in the hippocampus and the cerebellum of toluene-intoxicated rats. Basic-FGF may have induced GFAP expression both in the hippocampus and the cerebellum. So, other neurotrophic factors may affect the difference of GFAP elevation between the hippocampus and the cerebellum. These differences may relate to neurobehavioral function of each brain part after toluene exposure.

Acute Disease↗