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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mild case of self-poisoning with a chlorpyrifos formulation following oral ingestion is reported. A 15-year-old female went to the emergency room after the ingestion of a product from a bottle marked with a label "Poison". On admission, she was obtunded, with normal vital signs and a strong smell of solvent. Therapeutic measures included the application of decontamination procedures, oxygen, and gastric protectors. She had a good outcome with mild CNS depression and bradycardia. Two hours after ingestion, biological samples were collected in the emergency room and sent for analysis to our laboratory with instructions to investigate the presence of solvents. The serum and gastric content contained 5.3 and 9.4 microg/mL of unmetabolized chlorpyrifos, 4.6 and 6.9 microg/mL of toluene, and 2.5 and 7.9 microg/mL of butyl acetate, respectively. Small traces of other solvents and tetradifon were also detected. Toxicological analyses were negative for ethanol, other volatile solvents, and common drugs of abuse. The simultaneous determination of chlorpyrifos, toluene, and butyl acetate was performed using the combination of gas chromatography (GC)-flame ionization detection for screening analysis and GC-mass spectrometry for confirmation of the obtained results. The method provides an excellent and rapid tool for use in cases of pesticide poisonings, allowing the simultaneous detection of the pesticide and distillates in the performance of systematic toxicological analysis in forensic and clinical laboratories.
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PMID:Attempted suicide by ingestion of chlorpyrifos: identification in serum and gastric content by GC-FID/GC-MS. 1551 21

Physiologically based pharmacokinetic (PBPK) models have often been used to describe the absorption, distribution, metabolism, and excretion of chemicals in animals but have been limited to single chemicals and simple mixtures due to the numerous parameters required in the models. To overcome the barrier to modeling more complex mixtures, we used a chemical lumping approach, used in the past in chemical engineering but not in pharmacokinetic modeling, in a rat PBPK model for gasoline hydrocarbons. Our previous gasoline model consisted of five individual components (benzene, toluene, ethylbenzene, xylene, and hexane) and a lumped chemical that included all remaining components of whole gasoline. Despite being comprised of hundreds of components, the lumped component could be described using a single set of chemical parameters that depended on the blend of gasoline. In the present study, we extend this approach to evaporative fractions of gasoline. The PBPK model described the pharmacokinetics of all of the volatility-weighted fractions of gasoline when differences in partitioning and metabolism between fractions were taken into account. Adjusting the ventilation rate parameter to account for respiratory depression at high exposures also allowed a much improved description of the data. At high exposure levels, gasoline components competitively inhibit each other's metabolism, and the model successfully accounted for binary interactions of this type, including between the lumped component and the five other chemicals. The model serves as a first example of how the engineering concept of chemical lumping can be used in pharmacokinetics.
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PMID:Development of a physiologically based pharmacokinetic model for volatile fractions of gasoline using chemical lumping analysis. 1557 87

This review assesses the evidence regarding the effects of occupational exposure to organic solvents on colour discrimination and investigates exposure-response relationships and reversibility. This review also considers the current state of knowledge of the possible mechanisms underlying changes in colour vision, and the human health significance of any reported changes. Among the commonly used organic solvents, styrene has been investigated the most thoroughly. Studies of styrene-exposed workers in Germany, Italy and Japan provide a sufficiently consistent body of evidence to support a robust conclusion that styrene does cause an impairment of colour discrimination relative to age-matched controls. Generally, the impairment of colour discrimination observed in styrene-exposed workers tends to be of the tritan (blue-yellow) type, although some cases of red-green impairment have also been found. The limited information available on exposure-response relationships indicates that the effects on colour discrimination would not be expected at 8-hour time weighted average (8 h TWA) exposures <20 ppm, although a precise threshold cannot be determined. The data on reversibility are limited and inconclusive. The results from the most rigorous study in which this aspect was investigated point to a reversibility of effects after a 4-week exposure-free period, whereas results from a study with limitations suggest a persistence of effect. The effects of toluene, tetrachloroethylene or mixed solvent exposure have also been investigated, although the information available is generally less reliable than for styrene. For toluene, it can be confidently concluded that this solvent does not have an acute effect on colour discrimination, even when exposures are relatively high (50-150 ppm 8 h TWA, and 290-360 ppm 30 minutes TWA). However, studies are inconclusive on whether long-term or repeated exposure to toluene can cause a persistent impairment of colour discrimination. There are few studies that have specifically investigated the effects of tetrachloroethylene on colour discrimination. Among these studies, none has examined the potential for any acute effects of this solvent vapour. A large-scale study in Japanese workers showed no effects of long-term exposure to tetrachloroethylene concentrations in the region of 12-13 ppm. However, the test methodology used was relatively insensitive to changes in colour discrimination, hence the results do not provide reassurance for an absence of subtle effects. A study in Italian dry-cleaners suggested a slight impairment of colour discrimination relative to controls, associated with relatively low exposures to tetrachloroethylene (mean 8 h TWA exposure approximately 6 ppm). The studies concerning the effects of mixed solvent exposure on colour discrimination are based on workers exposed to solvents in paints and lacquers, workers from the printing and petrochemical industries, people working in or living near to microelectronics factories and children exposed to solvents prenatally. However, these studies are subject to design limitations or methodological irregularities, such that no conclusions regarding the effects of mixed solvent exposure on colour discrimination can be drawn. Overall, the only credible evidence for an effect of solvents on colour discrimination derives from the studies on styrene. Because of limitations in the data for other solvents it is not possible to determine whether the evidence for styrene reflects a generic property of solvents. The mechanisms of styrene-induced effects on colour discrimination have not been properly investigated and can only be the subject of speculation. One conclusion that can be drawn is that pathological changes to the ocular system, such as changes to the lens, are unlikely to be involved. This is because there is an absence of convincing evidence for such changes from medical examinations conducted in epidemiological studies of solvent-exposed workers. Also, it seems unlikely that effects on colour discrimination are a nonspecific consequence of more generalised CNS depression, given that styrene-induced effects on colour discrimination appear to occur below the threshold for narcotic effects. The effects of styrene on colour discrimination are subtle and involve an impairment of the ability to discriminate accurately between closely related shades of the same colour rather than 'colour blindness'. There is no valid basis for using colour discrimination as a marker for other forms of solvent-induced neurotoxicity.
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PMID:Does occupational exposure to organic solvents affect colour discrimination? 1557 64

When a solvent drop evaporates from a polymer surface, it leaves behind a characteristic structure, typically a crater. We deposited toluene drops with a microsyringe onto planar polystyrene (PS) surfaces and analyzed the surface topography after drying. For low molar mass PS (Mw = 20.9-24.3 kDa) dotlike protrusions with a ridge at the periphery formed on the polymer surface. With increasing molar mass the central region decreased in height. At Mw = 29.6-643 kDa a craterlike structure with a depression in the center and a ridge was observed. At even higher molar mass, irregular structures without rotational symmetry occurred. We explain the observed dependence on the molar mass with a different degree of entanglement, leading to different dissolution rates and different diffusion constants.
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PMID:Microstructures by solvent drop evaporation on polymer surfaces: dependence on molar mass. 1715 31

Acute exposure to toluene and other volatile organic solvents results in neurotoxicity characterized by nervous system depression, cognitive and motor impairment, and alterations in visual function. In vitro, toluene disrupts the function of N-methyl-D-aspartate (NMDA)-glutamate receptors, indicating that effects on NMDA receptor function may contribute to toluene neurotoxicity. NMDA-glutamate receptors are widely present in the visual system and contribute to pattern-elicited visual-evoked potentials (VEPs) in rodents, a measure that is altered by toluene exposure. The present study tested the hypothesis that effects on NMDA receptors contribute to toluene-induced alterations in pattern-elicited VEPs. Prior to examining the effects of NMDA receptor agonists and antagonists on toluene-exposed animals, a dose-range study was conducted to determine the optimal dose for NMDA (agonist) and MK801 (antagonist). Dose levels of 2.5 mg/kg NMDA and 0.1 mg/kg MK801 were selected from these initial studies. In the second study, Long-Evans rats were exposed to toluene by inhalation, and VEPs were measured during toluene exposure in the presence or absence of NMDA or MK801. Pattern-elicited VEPs were collected by exposing rats to a sinusoidal pattern modulated at a temporal frequency of 4.55 Hz. Following collection of baseline VEPs, rats were injected with either saline, NMDA (2.5 mg/kg, ip), or MK801 (0.1 mg/kg, ip) and 10 min later were exposed to air or toluene (2000 ppm). VEP amplitudes were calculated for 1x (F1) and 2x stimulus frequency (F2). The F2 amplitude was reduced by approximately 60, 60, and 50% in the toluene-exposed groups (TOL): SALINE/TOL (n = 11), NMDA/TOL (2.5 mg/kg; n = 13), and NMDA/TOL (10 mg/kg, n = 11), respectively. Thus, NMDA (2.5 and 10 mg/kg) did not significantly affect toluene-mediated F2 amplitude effects. Administration of 0.1 mg/kg MK801 prior to toluene exposure blocked the F2 amplitude decreases caused by toluene (n = 9). However, when 0.1 mg/kg MK801 was administered 20 min after the onset of toluene exposure, toluene-mediated F2 amplitude decreases persisted despite the challenge by MK801. These data support the hypothesis that acute actions of toluene on pattern-elicited VEPs involve NMDA receptors.
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PMID:Evaluating the NMDA-glutamate receptor as a site of action for toluene, in vivo. 1742 Feb 19

In this review, the recent findings of central nervous system (CNS) or peripheral nervous system (PNS) dysfunction induced by occupational exposure to organic solvents are described. While acute, high-level exposure to almost all organic solvents causes the general, nonspecific depression of CNS, it is still not clear whether chronic, low-level occupational exposure causes the chronic neurological dysfunction which has been called "organic solvent syndrome", "painters syndrome", "psycho-organic syndrome" or "chronic solvent encephalopathy". At least at lower than occupational exposure limits, chronic and low-level organic solvent exposure does not appear to cause the "sy mptomatic" neurological dysfunction. The chronic, moderate- to high-level exposure to a few organic solvents (such as carbon disulfide, n-hexane and methyl n-butyl ketone) affects CNS or PNS specifically. The substitutes for chlorofluorocarbons, 2-bromopropane and 1-bromopropane were shown to have the peripheral nerve toxicity in the experimental animals. Shortly after these observations, human cases of 1-bromopropane intoxication with the dysfunction of CNS and PNS were reported in the United States. Neurological abnormalities in workers of a 1-bromopropane factory in China were also reported. Thus, the possible neurotoxicity of newly introduced substitutes for ozone-depleting solvents into the workplace must be considered. Enough evidences indicate that some common solvents (such as toluene and styrene) induce sensorineural hearing loss and acquired color vision disturbances in workers. In some studies using magnetic resonance imaging (MRI), cerebral atrophy, patchy periventricular hyperintensities and hypointensities in the basal ganglia were found in solvent-exposed workers as have been shown in toluene abusers (toluene leukoencephalopathy). Further studies using the neurobehavioral test batteries, neurophysiological measurements and advanced neuroimaging techniques are required to detect the "subclinical" dysfunction of nervous systems in workers exposed to organic solvents at low-level.
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PMID:[Neurotoxicity of organic solvents--recent findings]. 1758 90

Abused inhalants are widely used, especially among school-age children and teenagers, and are 'gateway' drugs leading to the abuse of alcohol and other addictive substances. In spite of this widespread use, little is known about the effects produced by inhalants on the central nervous system. The similarity in behavioral effects produced by inhalants and inhaled anesthetics, together with their common chemical features, prompted this study of inhalant actions on a well-characterized anesthetic target, GABA synapses. Whole-cell patch clamp recordings were conducted on CA1 pyramidal neurons in rat hippocampal brain slices to measure effects on resting membrane properties, action potential discharge, and GABA-mediated inhibitory responses. Toluene, 1,1,1-trichloroethane, and trichloroethylene depressed CA1 excitability in a concentration-dependent and reversible manner. This depression appeared to involve enhanced GABA-mediated inhibition, evident in its reversal by a GABA receptor antagonist. Consistent with this, the abused inhalants increased inhibitory postsynaptic potentials produced using minimal stimulation of stratum radiatum inputs to CA1 neurons, in the presence of CNQX and APV to block excitatory synaptic responses and GGP to block GABA(B) responses. The enhanced inhibition appeared to come about by a presynaptic action on GABA nerve terminals, because spontaneous inhibitory postsynaptic current (IPSC) frequency was increased with no change in the amplitude of postsynaptic currents, both in the presence and absence of tetrodotoxin used to block interneuron action potentials and cadmium used to block calcium influx into nerve terminals. The toluene-induced increase in mIPSC frequency was blocked by dantrolene or ryanodine, indicating that the abused inhalant acted to increase the release of calcium from intracellular nerve terminal stores. This presynaptic action produced by abused inhalants is shared by inhaled anesthetics and would contribute to the altered behavioral effects produced by both classes of drugs, and could be especially important in the context of a disruption of learning and memory by abused inhalants.
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PMID:Abused inhalants enhance GABA-mediated synaptic inhibition. 1949 4

Toluene, a representative industrial solvent and abused inhalant, decreases neuronal activity in vitro and causes mental depression and cognitive impairment in humans. However, the effects of toluene on brain function and the sites of its action are poorly understood. This study investigated the temporal changes of neurogenesis in the hippocampus of adult C57BL/6 mice after acute administration of toluene using two immunohistochemical markers for neurogenesis, Ki-67 and doublecortin (DCX). In addition, after toluene treatment, depression-like behaviors and learning and memory tasks were examined to assess hippocampal neurogenesis-related behavioral dysfunction. The number of Ki-67- and DCX-positive cells in the dentate gyrus of adult hippocampi declined acutely between 0 h and 24 h after toluene treatment (500 mg/kg, i.p.) and increased gradually from 2 to 8 days post-administration. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of toluene administered (0-1000 mg/kg). In tail suspension and forced-swim tests performed at 1 and 4 days after toluene treatment (500 mg/kg), mice showed significant depression-like behaviors compared to the vehicle-treated controls. In the contextual fear conditioning and object recognition memory test, the mice trained at 1 and 4 days after toluene treatment showed significant memory defects compared to the vehicle-treated controls. This study suggests that acute exposure to toluene reduces the rate of adult hippocampal neurogenesis and can cause hippocampal dysfunction such as depression and cognitive impairment.
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PMID:Toluene inhibits hippocampal neurogenesis in adult mice. 1996 16

Whether long-term occupational exposure to organic solvents may affect mental and cognitive functioning later in life, remains unclear. In this study, twelve rotogravure printers formerly exposed to toluene and 19 referents, all initially examined in the mid-1980s, were reexamined after twenty years, applying neuropsychological tests, symptoms and social interaction questionnaires, medical examination, and exposure assessment of each individual's cumulative exposure. By far the most extensive exposure, mainly toluene, had occurred before 1985. The printers were found to have deteriorated more than their referents in cognitive functioning affecting reasoning and associative learning. No relevant additional exposure during the lengthy time period between assessments could explain this discrepancy. In addition, printers performed significantly worse than the referents in verbal memory and sustained attention at follow-up, where also a dose-effect relationship was noted for reasoning. While the printers did not report more subjective cognitive complaints than the referents, a slightly higher depression score was noted for the printers. The findings of significantly worse deteriorations in cognitive functioning in previously toluene-exposed printers are in line with our hypothesis that sub-clinical deficits during the working life may become manifest later in life, indicating that exposure may in fact interact with ageing. However, considering the small study groups the results must be interpreted with caution.
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PMID:Delayed manifestations of CNS effects in formerly exposed printers--a 20-year follow-up. 2058 Aug 17

Occupational medicine has always been part of social medicine, but focuses on the part of the population in paid employment. Investigations of occupational diseases have identified several toxic chemicals that can affect other sectors of society: examples include cancers due to sawdust, asbestos, benzene, as well as carcinogens, mutagens and reproductive toxins. Better knowledge of the risks posed by epoxy resins, cements, formaldehyde, lead, toluene and other chemical agents has helped to understand certain diseases in the population. Knowledge of musculoskeletal disorders due to repetitive work has been of help in other areas; gradual resumption of appropriate activity seems to be the best basic treatment. Studies of mental overload and its consequences in the workplace (suicide, depression, etc.) have implications for human relations in society as a whole. Multidisciplinary networking helps to regularly take stock of findings in occupational medicine that may be applicable to social medicine.
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PMID:[Contribution of occupational medicine to social medicine]. 2156 51


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