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PubMed1976

A compact, versatile inhalation exposure chamber for small animal studies.

An inhalation exposure chamber was designed to fit conveniently into a standard laboratory exhaust hood. The chamber was constructed entirely of non-corrosive materials and was suitable for continuous exposure of 6 small laboratory animals to corrosive atmospheres such as ozone. A separate, outer chamber surrounding a smaller, inner chamber permitted access to each individually housed animal without disturbing the experimental atmosphere. Facilities were available for ad libitum access to food and water for chronic exposures. The chamber was easily disassembled for cleaning. A safety mechanism was described which automatically stops the generation of a toxic gas in the event of an exhaust system failure.

Animals↗
PubMed1999

Effects of inhalation exposures to an M1-receptor agonist on ventilation in rhesus monkeys.

Information was needed on effects of possible occupational inhalation exposure to an M1-receptor agonist (xanomeline) such as might occur during the manufacturing process. Both acute and repeated inhalation exposures to xanomeline were carried out in six male rhesus monkeys using a head-dome exposure system. Exposure concentrations ranged from 0.3 to 10 mg/m3. The exposure durations were up to 2 weeks. Decreases in tidal volume and increases in respiratory frequency were both time and concentration related during acute exposures. These effects were blocked with atropine pre-treatment. Correlation with pulmonary resistance measurements in two monkeys suggested that these were bronchoconstrictive changes that increased with severity with time at a given concentration and with concentration when measured after a constant exposure time. The dose-response was relatively steep with 10 mg/m3 becoming intolerable to the monkeys after approximately 15 minutes, but no measurable effects were observed at 0.3 mg/m3 after up to 4 hours of exposure. To investigate the effects of repeated exposures, monkeys were exposed for 4 hr/day, 5 days/wk for 2 weeks to 0.0 (air only), 0.3, and 1.2 mg xanomeline/m3 of air. When compared to the air-only exposure, 0.3 mg/m3 caused no significant changes in tidal volume. In contrast, 1.2 mg/m3 caused a rapid and significant decrease in tidal volume that was sustained throughout the 4-hr exposure. A slower rise in breathing frequency also occurred. Repeated exposures did not alter the effects seen after a single exposure. It is concluded that xanomeline, a M1-receptor agonist, can acutely alter normal ventilation in non-human primates at airborne concentrations > or = 0.6 mg/m3 and should be carefully controlled in a manufacturing environment. The no-observed-effect concentration was 0.3 mg/m3.

Administration, Inhalation↗
PubMed1987

Inhalation exposure technology used for varying exposure modes and profiles in toxicology studies.

Current technology used in inhalation toxicology studies employs various exposure modes and concentration profiles. Inhalation exposure modes typically utilize wholebody techniques, whereas other exposure modes include nose- and head-only exposure systems and, in some cases, whole- or partial-lung exposure systems. The latter two conditions are utilized when safety considerations are warranted by the hazardous nature of the chemical or agent being tested, the test substance may be dermally adsorbed, and/or the costs of the chemical used are of concern. Inhalation exposure studies may span several minutes to 24 h of continuous exposure and from one day to the full life span of the animal being tested. Time-varying profile exposures, on the other hand, are typically used to mimic human exposures to chemical agents and, in some cases, to more accurately extrapolate animal toxicity data in assessing human risk. Automation of inhalation exposure systems has expedited the timely operation of both accurate and repeatable profiles, and it has allowed for reexamination of classical time-weighted average concentration information relating to human health concerns. The toxicological assessment of potential health effects resulting from exposure to airborne substances typically involves thorough characterizing of the test agent via acute, subchronic, and chronic toxicity testing.

Administration, Inhalation↗
PubMed1995

Pulmonary carcinogenicity of repeated inhalation exposure of rats to aerosols of 239PuO2.

To study the long-term biological effects of repeated inhalation exposure to 239PuO2, 84-day-old rats were exposed to aerosols of 239PuO2 to re-establish desired 239Pu lung burdens of 26, 80 or 250 Bq every other month for 1 year (seven exposures). Other rats were exposed once at 84 or 450 days of age to achieve desired initial lung burdens of 30, 90, 280 or 850 Bq. The incidences of lung tumors were not significantly different (Fisher's exact test; P > 0.05) in groups of rats with similar lifetime mean alpha-particle doses to the lungs of 0.90 +/- 0.39 to 4.4 +/- 1.8 (+/- SD) Gy, whether exposed once or repeatedly. Among rats with mean alpha-particle doses of 12 +/- 2.4 to 10 +/- 2.1 Gy to the lungs after single or repeated exposures, respectively, the crude incidence of lung tumors was significantly less (Fisher's exact test; P < 0.05) in the rats exposed repeatedly. Times to death of rats with lung tumors were compared among groups with similar alpha-particle doses to the lungs after single or repeated exposure to 239PuO2. Those that died with lung tumors after repeated exposures died at times similar to (Mantel-Cox statistic; P > 0.05) or later than (Mantel-Cox statistic; P < 0.05) those for 84-day-old rats exposed once. The risk of lung tumors in rats per unit dose to the lungs was less in the rats exposed repeatedly than in those exposed once. It was concluded that alpha-particle doses to the lung of rats exposed repeatedly to aerosols of 239PuO2 were not more carcinogenic and possibly were less carcinogenic than the dose after a single inhalation exposure when rats with similar lifetime alpha-particle doses to the lungs were compared. The relative biological effectiveness in rats of the alpha-particle dose to the lungs from inhaled 239PuO2 relative to beta-particle doses to the lungs from inhaled 144CeO2 was 21 +/- 3.

Administration, Inhalation↗
PubMed2006

Decreased expression of inflammation-related genes following inhalation exposure to manganese.

Excessive exposure to manganese (Mn) by inhalation can induce psychosis and Parkinsonism. The clinical manifestations of Mn neurotoxicity have been related to numerous physiological and cellular processes, most notably dopamine depletion. However, few studies have explored the molecular events that are triggered in response to exposure to Mn by inhalation. In this current study, the transcriptional patterns of genes related to oxidative stress or inflammation were examined in the brain rats of exposed to inhaled Mn during either gestation or early adulthood. The expression of genes encoding for proteins critical to an inflammatory response and/or possessing pro-oxidant properties, including TGFbeta and nNOS, were slightly depressed by prenatal exposure, whereas inhalation exposure to Mn during adulthood markedly down-regulated their transcription. However, when exposures to manganese occurred during gestation, the extent of altered gene expression induced by subsequent exposure to Mn in adulthood was reduced. This suggests that prior exposure to Mn may have attenuated the effects of inhalation exposure to Mn in adulthood, in which the expression of inflammation-related genes were suppressed.

Amyloid beta-Protein Precursor↗
PubMed1993

Dimethylformamide pharmacokinetics following inhalation exposures to rats and mice.

Whole-body inhalation exposures to N,N-dimethylformamide (DMF) were conducted with rats and mice. The exposure concentrations were 10, 250, and 500 ppm DMF. The exposure routines consisted of single 1-, 3-, or 6-hour exposures and ten 6-hour exposures (ten exposure days in 2 weeks). Area under the plasma concentration curve (AUC) values were determined following exposure for DMF and "N-methylformamide" ["NMF" represented N-methylformamide plus N-(hydroxymethyl)-N-methylformamide (DMF-OH)]. The DMF AUC values increased 8- and 29-fold for rats and mice, respectively, following single six-hour exposures to 250 and 500 ppm DMF. These data are indicative of saturation of DMF metabolism. Peak "NMF" plasma concentrations for rats and mice, following single 6-hour exposures, did not increase as DMF exposure concentrations increased from 250 to 500 ppm. In addition, the "NMF" plasma levels in rats following a single 6-hour 500 ppm DMF exposure did not decay by 24 hours post exposure. These "NMF" plasma data also indicate saturation of DMF metabolism. Multiple exposures to 500 ppm DMF resulted in a 3- and 4-fold reduction in DMF AUC values for rats and mice, respectively, compared to AUC values following a single six-hour 500 ppm DMF exposure. This indicates enhanced metabolism of DMF resulting from multiple 500 ppm DMF exposures and together with saturation of DMF metabolism suggest using exposure levels below 500 ppm in a chronic bioassay. Selected plasma samples were simultaneously assayed for NMF and DMF-OH. The "NMF" values consisted of between 30 to 60 percent DMF-OH depending upon the exposure group (conversely NMF represented 30 to 60 percent of the "NMF" levels). Urinary analysis of all samples revealed DMF-OH represented over 90 percent of the summed DMF, DMF-OH and NMF quantities.

Administration, Inhalation↗
PubMed1988

Respiratory tract lesions in F344/N rats and B6C3F1 mice after inhalation exposure to 1,2-epoxybutane.

1,2-Epoxybutane, a short-chain epoxide used as a stabilizer in chlorinated hydrocarbon solvents, was administered by inhalation exposure as a vapor 6 h/day, 5 day/week, for 24 months at exposure concentrations of 0, 200 or 400 ppm to F344/N rats and 0, 50, or 100 ppm to B6C3F1 mice. Survival of all groups of rats was 50% or greater until week 98 but was reduced in exposed groups by the end of the study. Survival in male mice was comparable among groups. Survival in female mice was greater than 50% until week 86, but was then reduced in the high-exposure group of mice. Exposure-related inflammatory, degenerative, and proliferative lesions occurred in the nasal cavity of both rats and mice. Seven papillary adenomas occurred in the nasal passages of high-exposure male rats and 2 in the nasal passages of high-exposure female rats. Alveolar/bronchiolar adenoma or carcinoma (combined) occurred with increased incidence in exposed male rats relative to controls. No exposure-related neoplastic lesions were seen in mice. After inhalation exposure, 1,2-epoxybutane was carcinogenic in rodents as were other epoxides or related compounds including propylene oxide, 1,3-butadiene, and ethylene oxide. The site of carcinogenic activity was considered to be related to length of the carbon chain.

Administration, Inhalation↗
PubMed1978

Differences following skin or inhalation exposure in the absorption and excretion kinetics of trichloroethylene and toluene.

The concentrations of trichloroethylene in breath and blood and the urinary excretion of its metabolites following 30 minutes' direct immersion of one hand in the liquid, were compared with those obtained after four hours' inhalation exposure to the vapour of 100 ppm, described in a previous paper. The comparison shows that the end-tidal air concentrations during the first two hours of the post-exposure period were about twice as high in the case of skin exposure as in that of inhalation exposure, although the uptake of the solvent through the skin was only about one-third of the inhaled uptake. A kinetic approach suggested that differences in trichloroethylene movement in the body would be a principal cause of this discrepancy. The results of a similar series of experiments using toluene suggested that it is less readily taken up than trichloroethylene through the skin. It was concluded from the present investigation that analyses of not only breath but also of blood or urine are necessary and toluene would rarely be absorbed through the skin in toxic quantities during normal industrial use.

Adult↗
PubMedDate not supplied

[Microsomal monooxygenases upon inhalation exposure to pseudocumene and durene].

This paper gives data on the levels of cytochromes of B5, P450, P420, P450 + P420, on the rates of amidopyrinum N-demethylation and aniline n-hydroxylation in the tissues of the lung, liver, kidney of experimental rats upon acute and chronic (4-month) inhalation exposure to pseudocumol and durol at a concentration of 10 mg/m3. Acute and chronic inhalation exposures to the xenobiotics in this concentration result in activation of microsomal monooxygenases in the tissues of experimental rats in relation to the type of exposure.

Animals↗
PubMed1994

Dimethylacetamide pharmacokinetics following inhalation exposures to rats and mice.

Whole-body inhalation exposures to N,N-dimethylacetamide (DMAC) were conducted with male rats (Crl:CD BR) and mice (Crl:CD-1 (ICR)BR). Exposure concentrations were 50, 150, 300 and 500 ppm. The exposure routines consisted of single 1-, 3-, or 6-h exposures and ten 6-h exposures (10 exposure days in 2 weeks). Area under the plasma concentration curve (AUC) values were determined for DMAC and its metabolite N-methylacetamide (NMAC), following 6-h exposures (single exposure or last in a series of 10 exposures). The range of exposures was chosen to assess the exposure-dependent nature of DMAC pharmacokinetics in rats and mice. Plasma profiles indicated mice metabolized DMAC rapidly with plasma half-lives from 0.3 to 0.5 h for DMAC. The DMAC AUC values from mice were underestimated due to the required time (< 30 min) between termination of exposure and the initial blood sample. DMAC plasma half-life in rats ranged from 0.6 to 1.5 h. The AUC values for DMAC in rats increased approximately 5-fold and 3-fold as exposure concentrations increased from 150 to 300 ppm and 300 to 500 ppm, respectively. NMAC persisted in plasma for at least 24 h after the 150, 300 and 500 ppm exposures to rats. NMAC was not detected in plasma from mice beyond the 12-h post-exposure timepoint for the 300 and 500 ppm exposures. Regardless of exposure level, repeated DMAC exposures to both rats and mice resulted in plasma profiles of DMAC and NMAC similar to those from a single exposure. The dose-dependent nature of the DMAC AUC data and the absence of effects of repeated 300 and 500 ppm DMAC exposures supported a toxicity-driven upper limit of 350 ppm for a chronic inhalation study.

Acetamides↗
PubMed1996

Evaluation of the mass balance model used by the Environmental Protection Agency for estimating inhalation exposure to new chemical substances.

The U.S. Environmental Protection Agency (EPA) is responsible for assessing the potential for unacceptable human health and environmental risks of new chemical substances prior to commercialization. Estimates of potential inhalation exposure to workers during manufacture, processing, and use of a new chemical substance are key elements of these assessments. However, the available information with which to assess the potential for exposure is often limited for new chemicals. One approach used by EPA to develop screening level estimates of inhalation exposure to vapors in the absence of data is the use of a mass balance model to predict the airborne concentration for various activities such as drumming and sampling. The mass balance model was evaluated by comparing the exposure estimates for specific operations with monitoring data reported in selected studies from the available literature. In general the estimated exposures based on the midpoint of the range of default input values were well within one order of magnitude of the measured exposures. Selection of more conservative (i.e., protective) model input values overestimated exposures by one or more orders of magnitude. There are many simplifying assumptions inherent in the model and many variables that influence exposure that are not considered. Uncertainty analyses of the model demonstrated that values selected for the ventilation flow rate and generation rate greatly influence the estimate of exposure and should be carefully chosen. Additional research is recommended, and ultimately, model validation should be completed to further improve and refine the model.

Air Pollutants↗
PubMed1998

Behavioural changes following a four-week inhalation exposure to hemimellitene (1,2,3-trimethylbenzene) in rats.

Trimethylbenzene isomers (TMBs): 1,2,4-TMB (pseudocumene--PS), 1,2,3-TMB (hemimellitene--HM) and 1,3,5-TMB (mesitylene--MES) are important constituents of solvent mixtures. In the US, the adopted TLV-TWA value for TMBs is 125 mg/m3 or 25 ppm (ACGIH 1996). Recent experiments at our laboratory have revealed an impaired learning of passive and active avoidance responses and a longer persistence of an effect of footshock (increase in latency of the paw-lick response to heat) in rats tested several weeks after a four-week inhalation exposure (6h/day, five days/week) to PS at a concentration of 100 or 250 ppm (15). The concentration-effect relationship appeared to be nonlinear; the effect of 100 ppm HM was more pronounced than that of 250 ppm. In the present experiment we investigated the effects of a repeated four-week (6h/day, 5 days/week) inhalation exposure to HM at concentrations of 0, 25, 100 or 250 ppm on radial-maze performance, open-field activity, passive and active avoidance learning, and on the shock-induced changes in latency of the paw-lick response to heat (hot-plate test). The tests were performed between days 14 and 61 after the last exposure. No significant effects on radial-maze performance and open-field activity were noted in any of the dose groups. In the remaining tests effects of exposure were noted but, similarly as in the case of PS exposure, the concentration-effect relationship was not linear. In rats exposed to HM at 25 or 100 ppm, but not 250 ppm, learning of the passive avoidance, i.e. refraining from performance of a punished response (stepping off an elevated platform) was significantly impaired. Moreover, in rats exposed to 100, but not 250 ppm of HM, acquisition of the two-way active avoidance in the shuttle-box was slower and the footshock-induced increase in latency of the paw-lick response to heat persisted longer than in the unexposed animals. The results suggest that a low-level inhalation exposure to HM, just like low-level exposure to PS, may lead to long-lasting disturbances in the CNS functions. The nonlinear concentration-effect relationship observed in the case of both TMB-s requires clarification in further studies.

Administration, Inhalation↗
PubMed2000

Pathogenetic process of lung tumors induced by inhalation exposures of rats to plutonium dioxide aerosols.

Sequential examinations were done on the pulmonary cytokinetics and pulmonary lesions in rats after inhalation exposure to (239)PuO(2) aerosols to investigate the pathogenesis of lung tumors. Total cell yields of lavaged bronchoalveolar cells as well as the estimated numbers of pulmonary alveolar macrophages were significantly reduced from 1 to 3 months after exposure but recovered thereafter to the control levels. The proportions of multinucleated or micronucleated pulmonary alveolar macrophages increased significantly in lavaged cells from 1 month, and the increase was sustained up to 18 months after exposure. Both tumor necrosis factor and nitric oxide were shown to be differentially released from stimulated cultures of pulmonary alveolar macrophages during the period from 6 to 18 months after exposure. The labeling indices of alveolar and bronchiolar epithelial cells treated with 5-bromo-2'-deoxyuridine increased significantly in lungs from 3 months and were sustained up to 18 months after exposure. Histopathological examinations revealed that after the early inflammation, hyperplasia and metaplasia of the lining of the bronchioloalveolar epithelium were predominant from 3 to 6 months, while adenomatous or adenocarcinomatous lesions appeared and developed from 12 months after exposure. The appearance of primary lung tumors, almost all of which were adenomas and adenocarcinomas, was found in the dose range of 1 to 2 Gy from 12 months after exposures. These results indicate that the pathogenetic process initiated by early cellular damage and alterations associated with inflammation is followed by the proliferative and metaplastic lesions of pulmonary epithelium, leading to the appearance and development of pulmonary neoplasms from 1 year after the inhalation exposures in rats that received a minimum lung dose of more than 1 Gy.

Adenocarcinoma↗
PubMed2004

Accidental dermal and inhalation exposure with fipronil--a case report.

BACKGROUND: Fipronil which has initiated the new generation of insecticides and possesses greater affinity at GABA receptors in insects than humans is supposed to be safer than the old generation of insecticides. Dermal and inhalation exposure to fipronil has not been reported in the literature. CASE REPORT: A 50-year-old male was admitted to the Clinic after 5h of spraying his field with the solution of fipronil. The patient was fully conscious with the BP and HR within normal range. There were no seizures, other neurological deficits, signs of conjunctivitis or skin irritation. Physical examinations and biochemical results were normal. The patient complained of a headache, nausea, vertigo and weakness. All symptoms resolved spontaneously after about 5h. During hospitalization and the follow up after three weeks he was asymptomatic. CONCLUSIONS: Further investigations should be carried on to evaluate the risk of fipronil in humans. The benzodiazepines are drugs of choice during seizures, B1 agonists and steroids may be useful during severe inhalation exposure.

Accidents, Occupational↗
PubMed1996

Pharmacological potency and biodisposition of phencyclidine via inhalation exposure in mice.

The purpose of the present study was to characterize the pharmacological effects and biodisposition of phencyclidine (PCP) following inhalation exposure to mice. Results from these studies indicate that PCP was easily volatilized when heated in a glass pipe. Volatilization was efficient with no significant formation of pyrolytic products. Exposure to the volatilized PCP resulted in a dose-dependent impairment in motor performance in both the rotorod and inverted-screen tests. PCP was equally effective in disrupting performance on the inverted-screen and rotorod with ED50 values corresponding to the volatilization of 10.7 and 13.2 mumol, respectively. The time courses were comparable to those produced following intravenous (i.v.) administration of PCP. In order to determine the dose of drug absorbed by inhalation, mice were exposed to [3H]-PCP. The ED50 values of PCP following i.v. administration were 4.1 and 6.2 mumol/kg in the inverted screen and rotorod, respectively. The biodisposition of PCP following inhalation exposure was similar to that after i.v. injections. At doses that produced approximately 50% of the maximum motor impairment by either administration route, higher ratios of the total drug equivalents were found following i.v. injection than that after inhalation, with the brain/plasma ratios of 1.3 +/- 0.2 versus 0.58 +/- 0.02, and brain/body ratios 0.59 +/- 0.06 versus 0.35 +/- 0.1 for i.v. and inhalation, respectively. However, the brain/plasma ratios of the concentrations of PCP were similar, 1.1 versus 0.9. The body concentration of PCP equivalents that produced 50% of the maximum effect after inhalation was 4.7 +/- 0.6 mumol/kg. These results indicate that inhalation of PCP produces a similar pharmacological profile to that of i.v. administration and suggest that the drug is equipotent by these two administrations routes. Moreover, these findings are consistent with the observation that smoking is becoming the most common route of administration among drug users.

Administration, Inhalation↗
PubMed2003

Pseudocumene in brain, liver, lung and blood of rats after single and repeated inhalation exposure.

Male Wistar rats were exposed to pseudocumene vapors at nominal concentration of 25, 100 or 250 ppm in the dynamic inhalation chambers for 6 h or 4 weeks (6 h/day; 5 days/week). Following the inhalation exposure, pseudocumene concentrations were estimated in the brain, liver and lung homogenates, as well as in the brain (brainstem, hippocampus, temporal cortex, cerebellum) and blood (arterial, venous) structures. To estimate pseudocumene concentrations in biological material gas chromatography using the headspace technique was applied. The elimination of pseudocumene from venous blood after repeated inhalation exposures followed an open two-compartment model. Venous blood concentration was about twice as high as that in arterial blood. In tissues, the highest values were found in the liver after single exposure to pseudocumene vapor at concentrations of 100 and 250 ppm. There were no statistically significant differences in pseudocumene concentrations between the brain, lungs or arterial blood. In the brain structures of the animals exposed to pseudocumene vapors, significantly higher concentration of psedocumene was found in the brainstem.

Administration, Inhalation↗
PubMed2006

Butyrylcholinesterase in guinea pig lung lavage: a novel biomarker to assess lung injury following inhalation exposure to nerve agent VX.

Respiratory disturbances play a central role in chemical warfare nerve agent (CWNA) induced toxicity; they are the starting point of mass casualty and the major cause of death. We developed a microinstillation technique of inhalation exposure to nerve agent VX and assessed lung injury by biochemical analysis of the bronchoalveolar lavage fluid (BALF). Here we demonstrate that normal guinea pig BALF has a significant amount of cholinesterase activity. Treatment with Huperzine A, a specific inhibitor of acetylcholinesterase (AChE), showed that a minor fraction of BALF cholinesterase is AChE. Furthermore, treatment with tetraisopropyl pyrophosphoramide (iso-OMPA), a specific inhibitor of butyrylcholinesterase (BChE), inhibited more than 90% of BChE activity, indicating the predominance of BChE in BALF. A predominance of BChE expression in the lung lavage was seen in both genders. Substrate specific inhibition indicated that nearly 30% of the cholinesterase in lung tissue homogenate is AChE. BALF and lung tissue AChE and BChE activities were strongly inhibited in guinea pigs exposed for 5 min to 70.4 and 90.4 microg/m3 VX and allowed to recover for 15 min. In contrast, BALF AChE activity was increased 63% and 128% and BChE activity was increased 77% and 88% after 24 h of recovery following 5 min inhalation exposure to 70.4 microg/m3 and 90.4 mg/m3 VX, respectively. The increase in BALF AChE and BChE activity was dose dependent. Since BChE is synthesized in the liver and present in the plasma, an increase in BALF indicates endothelial barrier injury and leakage of plasma into lung interstitium. Therefore, a measure of increased levels of AChE and BChE in the lung lavage can be used to determine the chronology of barrier damage as well as the extent of lung injury following exposure to chemical warfare nerve agents.

Acetylcholinesterase↗
PubMed2006

Changes in the function of the inhibitory neurotransmitter system in the rat brain following subchronic inhalation exposure to 1-bromopropane.

1-Bromopropane (1-BP) has been widely used as a cleaning agent and a solvent in industries, but the central neurotoxicity of 1-BP remains to be clarified. In the present study, we investigated the effects of subchronic inhalation exposure to 1-BP vapor on the function of the inhibitory neurotransmitter system mediated by gamma-aminobutyric acid (GABA) in the rat brain. Male Wistar rats were exposed to 1-BP vapor for 12 weeks (6h/day, 5 days/week) at a concentration of 400 ppm, and, in order to investigate the expression and function of brain GABA type A (GABAA) receptors, total/messenger RNA was prepared from the neocortex, hippocampus, and cerebellum of the control and 1-BP-exposed rats. Moreover, hippocampal slices were prepared, and the population spike (PS) amplitude and the slope of the field excitatory postsynaptic potential (fEPSP) were investigated in the paired-pulse configuration of the extracellular recording technique. Using the Xenopus oocyte expression system, we compared GABA concentration-response curves obtained from oocytes injected with brain subregional mRNAs of control and 1-BP exposed rats, and observed no significant differences in apparent GABA affinity. On the other hand, paired-pulse inhibition of PS amplitude was significantly decreased in the hippocampal dentate gyrus (DG) by exposure to 1-BP, without any effect on the paired-pulse ratio of the fEPSP slopes, suggesting neuronal disinhibition in the DG. Moreover, RT-PCR analysis indicated decreased levels of GABAA receptor beta3 and delta subunit mRNAs in the hippocampus of 1-BP-exposed rats. These results demonstrate that subchronic inhalation exposure to 1-BP vapor reduces the function of the hippocampal GABAergic system, which could be due to changes in the expression and function of GABAA receptors, especially the delta subunit-containing GABAA receptors.

Animals↗