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Objective: To investigate the changes in mass spectrometry of proteins in patients with 1-bromopropane (1-BP) poisoning after treatment and their biological functions. Methods: From May 2016 to December 2017, 3 male patients aged 31-47 years with 1-BP poisoning in Bao'an District of Shenzhen, China were enrolled in this study. The whole blood sample (2 ml) was collected before and after treatment. Label-free mass spectrometry-based proteomics was used for protein identification and quantification. The differentially expressed proteins after treatment were analyzed. Bioinformatics tools were used to analyze the functions of the identified proteins and the biological processes they were involved in. Results: Proteomic analysis showed that there were 47 proteins that were differentially expressed more than 2-fold ( P <0.05) after treatment in the patients with 1-BP poisoning; of them, 27 were up-regulated and 20 were down-regulated in the serum of treated patients. The identified proteins were mainly involved in proteolysis, protein modification, immune response, complement activation, lipoprotein metabolism, signal transduction, and coagulation. Conclusion: The differentially expressed proteins after treatment can help with the diagnosis, treatment, and prognosis monitoring of 1-BP poisoning and provide potential therapeutic and prognostic markers for 1-BP poisoning treatment.

1-Bromopropane (1-BP) is an increasingly used chemical solvent for cleaning metals and gradually replacing spraying adhesives. Workers exposed to 1-BP (WBP) showed nervous system dysfunction and other symptoms. This study focused on the proteomic change between healthy individuals (HIs), WBP and poisoned patients with 1-BP (PBP). Total proteins from serum samples were isolated, and high-abundance proteins were filtered out. Large-scale label-free proteomics platform was utilized for protein identification and quantitative comparison, followed by biological function analysis by bioinformatics tools. Compared to HI, 99 proteins were up-regulated and 55 proteins were down-regulated in WBP; 59 proteins were up-regulated and 94 proteins were down-regulated in PBP. With WBP as control, 63 proteins were up-regulated and 127 proteins were down-regulated in PBP. These differently expressed proteins were mainly involved in the immune response, neuron system regulation, blood coagulation, wound healing, endopeptidase activity, lipid metabolic process and apoptosis. The proteomic profiling change of HI, WBP and PBP provides a comprehensive view on 1-BP poison through immune response, signal transduction, metabolism, coagulation and response to stress. This study expanded our understanding on early development and maintenance and provided more potential protein markers for diagnosis of 1-BP poisoning.

Objective: To investigate the changes in protein expression in patients with 1-bromopropane (1-BP) poisoning using high-throughput proteomic technique and to screen out protein markers. Methods: Serum samples were collected from 3 patients with 1-BP poisoning and 15 controls. The label-free proteomic tech-nique was used for the quantitation and identification of proteins expressed in these samples, and the results were compared between the patients with 1-BP poisoning and the control population. The bioinformatics tools were used to analyze the function of differentially expressed proteins. Results: Compared with the control popula-tion, the patients with 1-BP poisoning had >2-fold upregulation of 38 proteins and >2-fold downregulation of 68 proteins. The differentially expressed proteins were mainly involved in immune response, signal transduction, and stress response. Conclusion: The proteins screened out may be potential protein markers for 1-BP poison-ing, which provides reliable and precise methods and thoughts for the diagnosis of 1-BP poisoning.

Objective: This study was mainly focused on styudy on he proteome profile change between exposure to 1-Bromopropane (1-BP) and 1-BP poisoning. Methods: The samples of serums from exposure to 1-BP and 1-BP poisoning were collected and analyzed through Label free proteome technology platform. The differently expressed proteins between the two groups were quantified and identified, followed by function analysis by bioinformatics. Results: 127 proteins over 2 fold-change were selected, in which 39 proteins were up-regulated and 88 proteins were down-regulated. These different-ly expressed proteins were mainly involved in the process of enzyme active regulation, inflammatory reaction, protein modification, stress response, coagulation, transport. Conclusion: The differently expressed proteins provided the potential protein biomarkers for the early diagnosis of 1-BP poisoning and was beneficial for clinical diagnosis of 1-BP and understanding of the mechanism of 1-BP poisoning.

Background: Brominated flame retardants (BFRs), are chemicals widely used in consumer products including electronics, vehicles, plastics and textiles to reduce flammability. Experimental animal studies have confirmed that these compounds may interfere with thyroid hormone homeostasis and neurodevelopment but to date health effects in humans have not been systematically examined., Objectives: To conduct a systematic review of studies on the health impacts of exposure to BFRs in humans, with a particular focus on children., Methods: A systematic review was conducted using the MEDLINE and EMBASE electronic databases up to 1 February 2012. Published cohort, cross-sectional, and case-control studies exploring the relationship between BFR exposure and various health outcomes were included., Results: In total, 36 epidemiological studies meeting the pre-determined inclusion criteria were included. Plausible outcomes associated with BFR exposure include diabetes, neurobehavioral and developmental disorders, cancer, reproductive health effects and alteration in thyroid function. Evidence for a causal relationship between exposure to BFRs and health outcomes was evaluated within the Bradford Hill framework., Conclusion: Although there is suggestive evidence that exposure to BFRs is harmful to health, further epidemiological investigations particularly among children, and long-term monitoring and surveillance of chemical impacts on humans are required to confirm these relationships., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Context: Methyl bromide is a halogenated aliphatic hydrocarbon that exists as a colorless gas or a volatile liquid. Methyl bromide historically had been used in fire extinguishers but is more commonly used as a gas fumigant for soil-borne diseases and pests. Methyl bromide is being phased out due to concerns for ozone depletion but can still be found. It is readily absorbed through the lungs while dermal absorption can also occur. Signs and symptoms of severe exposures include headache, respiratory distress, pulmonary hemorrhage, and seizures. In large pulmonary exposures, death can occur as rapidly as 1 h usually from respiratory failure. Methyl bromide can penetrate clothing and protective equipment presenting challenges to first responders. There is a debate over the mechanism of toxicity of methyl bromide and the role of hemodialysis and chelation in treatment., Case Details: A 22-year-old female employee of a fumigation company contacted emergency medical services (EMS) after opening a tank of compressed methyl bromide in her car. She was initially combative and confused. She underwent two water dermal decontaminations and was transported to the nearest tertiary center. She rapidly progressed to obtundation with seizure-like activity and dysrhythmias. Despite the supportive care and resuscitative efforts, she died approximately 1 h after her call to EMS., Discussion: Methyl bromide exposures can be fatal, and this case highlights the difficulty in managing these acutely poisoned patients. Questions for consideration after this case include time spent on decontamination, use of adjunctive anti-epileptic drugs, role of chelation therapy, and the role of hemodialysis in the treatment of methyl bromide poisoning.

Purpose: Methyl bromide is a genotoxic soil fumigant with high acute toxicity, but unknown human carcinogenicity. Although many countries have reduced methyl bromide use because of its ozone depleting properties, some uses remain in the United States and other countries, warranting further investigation of human health effects., Methods: We used Poisson regression to calculate rate ratios (RR) and 95 % confidence intervals (CI) for associations between methyl bromide use and all cancers combined, as well as 12 specific sites, among 53,588 Agricultural Health Study pesticide applicators with follow-up from 1993 to 2007. We also evaluated interactions with a family history for four common cancers (prostate, lung, colon, and lymphohematopoietic). We categorized methyl bromide exposure based on lifetime days applied weighted by an intensity score., Results: A total of 7,814 applicators (14.6 %) used methyl bromide, predominantly before enrollment. Based on 15 exposed cases, stomach cancer risk increased monotonically with increasing methyl bromide use (RR = 1.42; 95 % CI, 0.51-3.95 and RR = 3.13; 95 % CI, 1.25-7.80 for low and high use compared with no use; p (trend) = 0.02). No other sites displayed a significant monotonic pattern. Although we previously observed an association with prostate cancer (follow-up through 1999), the association did not persist with longer follow-up. We observed a nonsignificant elevated risk of prostate cancer with methyl bromide use among those with a family history of prostate cancer, but the interaction with a family history did not achieve statistical significance., Conclusions: Our results provide little evidence of methyl bromide associations with cancer risk for most sites examined; however, we observed a significant exposure-dependent increase in stomach cancer risk. Small numbers of exposed cases and declining methyl bromide use might have influenced our findings. Further study is needed in more recently exposed populations to expand on these results.

Methyl bromide (MeBr) is a toxic gas used to fumigate agricultural fields and some produce. The U.S. Department of Agriculture (USDA) requires MeBr fumigation of grapes imported from Chile to prevent invasion by the Chilean false red mite, Brevipalpus chilensis. In 2010, two workers were exposed intermittently to MeBr over several months as part of their job inspecting produce at a cold-storage facility in Carson, California. Both workers had disabling neurologic symptoms (e.g., ataxia, memory difficulties, and dizziness) and elevated serum bromide concentrations. An environmental investigation revealed the potential for MeBr to accumulate in enclosed areas during the transportation and storage of fumigated grapes. Some MeBr air concentrations measured at a single point in time exceeded current 8-hour exposure limits, suggesting that exposure in confined areas could result in poisoning. Possible measures for facilities managers to consider to reduce postfumigation MeBr exposures include 1) increased aeration time, 2) reduction of packaging that might absorb MeBr or limit aeration, and 3) changes in the stacking of pallets to improve air flow. Facilities should monitor air MeBr levels if they store MeBr-fumigated commodities in enclosed spaces entered by workers. Clinicians should consider occupational and environmental exposures in their differential diagnosis, and workers who might become exposed to fumigants should be informed of the health hazards related to these pesticides.

Background: A suspected inhalation exposure to methyl bromide (MeBr) in the packaging and shipping area of a chemical manufacturer resulted in a worker fatality and several symptomatic cases. However, air testing was negative for MeBr resulting in uncertainty regarding the potential chemical exposure. Methods of quickly confirming the exposure and magnitude were sought., Methods: Head space air and water samples were obtained from the breakroom water cooler in the facility and tested for MeBr., Results: Increased levels of MeBr were identified in the air and water samples from the cooler and used to calculate the MeBr concentration of air entering the cooler. The MeBr air concentration within the breakroom was estimated as 1,200-2,100 ppm depending on assumptions regarding the amount of water dispensed from the cooler both before and during the incident., Conclusions: Estimated MeBr air concentrations in the breakroom were consistent with those known to be associated with reported health effects among the involved workers. The water cooler analysis represented a unique method of retrospectively verifying and quantifying exposure to MeBr.

The port of Rotterdam, The Netherlands, is the world's largest container port. In 2006, one of these containers caused a chemical incident. Methylbromide is used in some countries as a pesticide for the fumigation of maritime containers. Because of an insufficiently performed detoxification, this insecticide intoxicated several employees and some of the ambulance crew and Mobile Medical Team (MMT). The victims displayed symptoms of sore throat, irritated eyes, and hypersalivation. One of the victims suffered from multiple epileptic seizures. Two victims were admitted to the intensive care unit for respiratory support. Three other employees showed milder symptoms and received supportive care but were not admitted to the hospital. This complicated case shows that the safety of the ambulance crew and MMT must be guaranteed. It also demonstrates that healthcare providers cannot always oversee the accident scene and that there are some pitfalls that are almost impossible to prevent.

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.

Background: 1-bromopropane was recently substituted for traditional ozone-depleting solvents in the industrial setting., Case Series: We report a cohort of six cases of 1-bromopropane neurotoxicity occurring in foam cushion gluers exposed to 1-bromopropane vapors from spray adhesives. Patients 1-5 were exposed 30-40 hours per week over three years; patient 6 had been employed for the previous three months. Exposure had peaked over the previous month when ventilatory fans were turned off. All patients complained of subacute onset of lower extremity pain or paresthesias. Five of six complained of difficulty walking and on examination had spastic paraparesis, distal sensory loss, and hyperreflexia. Three patients initially had nausea and headache. Serum bromide concentrations ranged from 44 to 170 mg/dL (reference 0-40 mg/dL). Apparent hyperchloremia was present with serum chloride concentrations of 105 to 139 mmol/L (reference 98-107 mmol/L). Air samples taken at the workplace during gluing operations revealed the mean air concentration of 1-bromopropane to be 130 ppm (range 91-176 ppm) with a seven hour time-weighted average of 108 ppm (range 92-127 ppm), well above the EPA-proposed limit of 25 ppm. Two years after exposure, the two most severely affected patients had minimal improvement of function and they, with a third patient, continued to experience chronic neuropathic pain., Conclusion: This report supports the growing recognition of 1-bromopropane neurotoxicity in humans consisting most commonly of headache, nausea, and subacute spastic paraparesis with distal sensory loss. The pathogenesis of 1-BP neurotoxicity in humans has yet to be fully elucidated but may reflect a central distal axonopathy syndrome.

Introduction: Methyl bromide is a pesticide used as a fumigating agent in homes, for food storage and soil disinfection. Chronic and acute exposures to methyl bromide are known to cause damage to the central and peripheral nervous system., Observation: We describe a case of a 31-year-old patient who developed a peripheral neuropathy due to an acute exposure on skin of methyl bromide. This patient was admitted after an accidental dermal exposure to methyl bromide while fumigating dates. The patient suffered dermal burns and vesicles on the upper limbs. Two weeks following exposure, she developed weakness of the lower and upper limbs, ataxia, paresthesiae of both legs and arms, abolition of tendon reflexes in the upper and lower limbs and Babinski sign. An axonal neuropathy was detected at the electrophysiological study. The patient recovered gradually., Conclusion: While cases of methyl bromide are rare, this study illustrates the toxic effect on the peripheral nervous system.

Methyl bromide is toxic to the central and peripheral nervous systems. A patient with occupational exposure to this agent is described. MRI showed strikingly symmetric brainstem and cerebellar lesions. The patient's clinical course and the topography and resolution of his MRI abnormalities suggest that this condition is an energy deprivation syndrome.

The Montreal Protocol on Substances that Deplete the Ozone Layer requires developed countries to phaseout methyl bromide production and non-quarantine uses by 2005 and developing countries to do the same by 2015. Exemptions to phaseout have been significant in slowing the process of abatement; many countries have applied for exemptions for some uses, partly on grounds that phaseout is economically infeasible. Data on the US strawberry market are used to investigate grower costs arising from substitution away from methyl bromide, the impact of trends in and characteristics of the demand for fresh strawberries, and characteristics of trade with countries not yet required to eliminate use of the compound. It appears that actual net costs to growers will be much smaller than the simple increase in production costs cited in the US nomination for exemption.

We reported recently that 1-bromopropane (1-BP; n-propylbromide, CAS Registry no. 106-94-5), an alternative to ozone-depleting solvents, is neurotoxic and exhibits reproductive toxicity in rats. The four most recent case reports suggested possible neurotoxicity of 1-BP in workers. The aim of the present study was to establish the neurologic effects of 1-BP in workers and examine the relationship with exposure levels. We surveyed 27 female workers in a 1-BP production factory and compared 23 of them with 23 age-matched workers in a beer factory as controls. The workers were interviewed and examined by neurologic, electrophysiologic, hematologic, biochemical, neurobehavioral, and postural sway tests. 1-BP exposure levels were estimated with passive samplers. Tests with a tuning fork showed diminished vibration sensation of the foot in 15 workers exposed to 1-BP but in none of the controls. 1-BP factory workers showed significantly longer distal latency in the tibial nerve than did the controls but no significant changes in motor nerve conduction velocity. Workers also displayed lower values in sensory nerve conduction velocity in the sural nerve, backward recalled digits, Benton visual memory test scores, pursuit aiming test scores, and five items of the Profile of Mood States (POMS) test (tension, depression, anxiety, fatigue, and confusion) compared with controls matched for age and education. Workers hired after May 1999, who were exposed to 1-BP only (workers hired before 1999 could have also been exposed to 2-BP), showed similar changes in vibration sense, distal latency, Benton test scores, and depression and fatigue in the POMS test. Time-weighted average exposure levels in the workers were 0.34-49.19 ppm. Exposure to 1-BP could adversely affect peripheral nerves or/and the central nervous system.

A nonlethal poisoning case by methyl bromide in a young woman due to leakage of old fire extinguishers is described. The patient developed major action and intention myoclonus the day following exposure. Inorganic bromide concentrations in plasma were determined by inductively coupled plasma mass spectrometry. The initial plasma bromide level was 202 mg/L, 40-fold in excess than the commonly accepted tolerance limit, and decreased slowly to normal levels within 2 months. Although plasma inorganic bromide concentration is known not to be directly correlated to the severity of organic bromide poisoning, its determination was, in the present case, particularly useful to confirm the diagnosis. One year post-exposure, the patient showed no sign of central nervous system toxicity. While such a case of poisoning is particularly rare today, it illustrates, however, that the danger still exists in France although the destruction

We encountered three patients (Patient I: 39-year-old man, Patient II: 34-year-old woman, and Patient III: 5-year-old girl) with acute methyl bromide poisoning, which had occurred as a result of exposure to the gas that leaked from methyl bromide cans stored in a warehouse of a seedling farm. Since all three patients exhibited almost the same initial symptoms, i.e., severe vomiting, tonic convulsions and clouding of consciousness, botulism was suspected at first. However, subsequent inquiry revealed that 27 cans of methyl bromide had been stored in the building that the patients lived in, and that the cans had been damaged a few days before the onset of the patients' illness by a thrashing machine that was being moved by them to another location. Inspection revealed that all the cans of methyl bromide had passed the expiry date and were corroded. Even though none of the cans had been used, three cans with a capacity of 750 g were found to be empty. Plasma bromide ion concentrations were determined to be high (72.9 microg/ml, 67.8 microg/ml and 91.5 microg/ml; normal level, < 5 microg/ml), and acute methyl bromide poisoning was diagnosed 8 days after admission of the patients to the hospital. Hemodialysis (peritoneal lavage in the case of the child) was performed immediately, after which the plasma bromide ion concentrations returned to normal and the general condition of the patients gradually improved.

Methyl bromide poisoning is difficult to confirm because routine laboratory testing has not been reliable. Measurable levels of the parent agent are rapidly reduced, probably as a result of direct tissue chemical reaction. Serum bromide levels have been used as an indirect measure of exposure and/or toxicity but are inconsistent. Recently special testing has shown that protein adducts formed after exposure to methyl bromide may be a better measure of significant exposure. The S-methylcysteine adduct was used to confirm acute methyl bromide toxicity 10 weeks after an exposure. Additionally, genotyping of the glutathione-S-transferase TI enzyme in erthyrocytes from this case characterized a predisposition to the neurotoxic effects of methyl bromide.

A 30-year-old man developed paresthesia in the feet, unstable gait and blepharoptosis subsequent to pharyngeal pain while working in a warehouse of imported fruit and vegetable fumigated with methyl bromide and cyanate. Neurological examination showed bilateral blepharoptosis, diplopia, ataxic gait and paresthesia below the inguinal region. The serum concentration of thiociane, a metabolite of cyanide, was within normal limits, but that of bromide was elevated (43.7 mg/l, normal: 3.7-8.6). Thus we diagnosed the patient as intoxication of methyl bromide. Magnetic resonance imaging of the brain (MRI) revealed bilateral symmetrical lesions of high signal intensity in the posterior region of the putamen, the subthalamic nuclei, the dorsal medulla oblongata corresponding to inferior cerebellar peduncles and vestibular nuclei, the inferior colliculi and the periaqueductal gray matter surrounding the oculomotor nucleus of the midbrain. As far as we know, this is the first report of MRI detected cerebral lesions in a case with intoxication of methyl bromide.

Case Report: We describe a case of early peripheral neuropathy and central nervous system toxicity as a result of acute predominantly dermal exposure to methyl bromide. A 32-year-old male was admitted after an accidental predominantly dermal exposure to methyl bromide while fumigating soil for pest control. The patient suffered dermal burns and vesicles on the upper and lower limbs. One week following exposure, he developed progressive weakness of the lower limbs, ataxia, paresthesiae of both legs and the left arm, hyperactive tendon reflexes in the lower limbs, and left Babinski sign. Nerve conduction velocity testing was compatible with axonal neuropathy. The patient recovered gradually from his burns. Three months postexposure he showed no signs of central nervous system toxicity, but the peripheral neuropathy was still present., Discussion: Neurological effects primarily referable to the central nervous system following severe inhalation of methyl bromide have frequently been reported. The patient described in this study developed an unusual early peripheral neuropathy following dermal exposure. Peripheral neuropathy can be an outcome of methyl bromide intoxication, but is usually a late sequela of acute central nervous system toxicity or an aftereffect of repetitively inhaled chronic exposure. In this case, exposure to methyl bromide through abraded skin caused early peripheral neuropathy and central nervous system toxicity.

A 19-year-old male developed complaints including weakness of the lower extremities and right hand, numbness, dysphagia and urinary difficulties following a 2 month exposure to an industrial solvent constituted mainly of 1-bromopropane, but also containing butylene oxide, 1,3 dioxolane, nitromethane, and other components. Nerve conduction studies revealed evidence of a primary, symmetric demyelinating polyneuropathy. Evidence of CNS involvement came from gadolinium enhanced MRI scans of the brain, showing patchy areas of increased T2 signal in the periventricular white matter, similar scans of the spinal cord revealing root enhancement at several lumbar levels, and SSEP studies. The patient's symptoms had started to resolve following the discontinuation of the exposure, before he was lost to follow-up. Similar findings have been reported following 1-bromopropane exposure in rats. I hypothesize that this patient's symptoms may have been due to 1-bromopropane-induced neurotoxicity.

Introduction: Methyl bromide has been responsible for deaths that usually occur from its accidental inhalation during fumigation., Case Report: We report an accidental fatality that occurred after methyl bromide seeped through underground conduits from a fumigated building to an adjacent guest house on the same property. The patient developed refractory seizures, intermittent fever, and multiorgan system failure before dying 19 days after exposure. The initial serum bromide was 27 mg/dL. Postmortem analysis detected methyl bromide concentrations of 2.9 mg/dL in the blood, 1.7 mg/dL in the bile, 24 micrograms/g in the liver, and 28 micrograms/g in the adipose tissue., Conclusion: Methyl bromide, although applied under acceptable safety standards, led to the inadvertent death of a young woman. Extreme care must be used when fumigating to insure no unsuspected seepage routes exist.

A case of fatal poisoning due to ingestion-inhalation of methyl bromide (MeBr) is presented. In previously reported fatalities due to MeBr inhalation, only inorganic bromide levels in biological specimens were reported. Intact MeBr has not been isolated from human tissues following exposure. In the present case, MeBr was detected, confirmed and quantitated in various biological samples by headspace gas chromatography, and the clinical manifestations and autopsy findings are described. Postmortem MeBr peripheral blood concentration was 3.3 micrograms/mL and in subclavian blood was 3.8 micrograms/mL. Lung, brain, adrenal gland, kidney, liver and testis MeBr was 2.9, 3.5, 3.4, 2.6, 1.9 and 2.8 micrograms/g respectively; MeBr in bile was 1.2 micrograms/mL. Inorganic bromide concentrations were 530, 30, 310 and 130 micrograms/g in blood, brain, kidney and adrenal gland respectively.

Objective: To examine all methyl bromide poisonings reported to the Marseille Poison Centre and to describe more precisely the infrequent cases of chronic, nonacute exposure., Design: Retrospective observational cohort., Method: Data retrieval from the French Poison Centres National Data Bank (ARIT) which contains all the cases of poisonings collected by the Marseille Poison Centre (Hot Line observations, Toxicovigilance, Toxicological intensive care unit). All methyl bromide poisonings 1973-1994 were examined to evaluate to frequency of the different circumstances., Results: Of the 89 methyl bromide intoxications studied, there were two cases of chronic exposure: two workers presented with neurological signs of cerebello-vestibular and pyramidal deficits, visual troubles and peripheral neuropathy of the lower limbs at the end of a season of exposure during which no acute incident involved. In one patient, the symptoms improved within five months; in the other, paresthesia were still present two years later and were associated with visual after-effects., Conclusion: The incidence of chronic methyl bromide intoxication is low. The risk for chronic exposure or persistent toxic effects may be masked by the severity of the acute toxic effects. The development of peripheral neuropathy immediately after the central neurological signs was noted in our two subjects. A dying back axonopathy may explain this unique chronological evolution.

Objectives: To determine the activity of glutathione transferase and to measure the S-methylcysteine adducts in blood proteins, after acute inhalation exposure to methyl bromide. To examine the influence of the polymorphism of glutathione-S-transferase theta (GSTT1) on the neurotoxicity of methyl bromide., Methods: Two workers acutely exposed to methyl bromide with inadequate respiratory protective devices were poisoned. Seven weeks after the accident, blood samples were drawn from both patients, for measurement of glutathione transferase activity in erythrocytes (conjugator status--that is, GSTT1 phenotype) and measurement of binding products of methyl bromide with blood proteins. Conjugator status was determined by a standard procedure. The binding product of methyl bromide, S-methylcysteine, was measured in globin and albumin., Results: Duration and intensity of exposure were identical for both patients as they worked together with the same protective devices and with similar physical effort. However, one patient had very severe poisoning, whereas the other only developed mild neurotoxic symptoms. The first patient was a "conjugator" with normal glutathone transferase activity, whereas this activity was undetectable in the erythrocytes of the second patient, who consequently had higher concentrations of S-methylcysteine adduct in albumin (149 v 91 nmol/g protein) and in globin (77 v 30 nmol/g protein)., Conclusions: Methyl bromide is genotoxic and neurotoxic. Its genotoxicity seems to be the consequence of the alkylating activity of the parent compound, and conjugation to glutathione has a protective effect. The data presented here suggest a different mechanism for methyl bromide neurotoxicity which could be related to the transformation of methylglutathione into toxic metabolites such as methanethiol and formaldehyde. If such metabolites are the ultimate toxic species, N-acetylcysteine treatment could have a toxifying rather than a detoxifying effect.

There have been over 300 cases of methyl bromide poisoning reported in the literature. The first objective of this case report was to bring out an experience with the false belief that work in a closed space is safe when accompanied by the use of a cartridge respirator with activated charcoal. The second objective of this article was to demonstrate the marked toxicity of methyl bromide with the potential to cause long-term neurological damage. Two experienced fumigation workers (equipped with rapidly saturable respiratory cartridges) entered a building where the concentration of methyl bromide was 17g x m-3 instead of the advised 20mg x m-3. They felt rapidly unwell and complained of nausea and shortness of breath, followed for one them by generalized convulsions. Five months later this last man was still bedridden. The other worker had almost no after-effects. The highest bromide level was found in the blood and also in the activated charcoal cartridge of the most injured worker. There was a relationship between methyl bromide level exposure and neurological damage importance.

Acute accidental methyl bromide poisoning was treated with haemodialysis. The treatment was successful in removing bromide from the blood but the patient persists with severe neuropsychiatric sequelae. To the best of our knowledge haemodialysis has not been used previously for the treatment of organic bromide poisoning.

Methyl bromide (MB) is a pesticide used primarily as a fumigating agent for homes, storage vehicles and soil. Chronic exposure to MB is known to cause damage to the central nervous system and other organs. Previously published post-mortem studies have also revealed significant brain abnormalities in patients whose deaths were attributed to MB. Only one study to date has examined the neuropsychological effects of this potential neurotoxin. The present case report documents the events surrounding an incident of acute and subacute MB exposure following home fumigation and the neuropsychological after-effects associated with that exposure. Behavioural and cognitive correlates of CNS dysfunction revealed by the neuropsychological testing included impairments in concentration, information processing, learning and memory. Emotional sequelae appeared to be a secondary problem associated with fears over physical well-being and impaired cognition. The cognitive symptomatology did not abate after completion of litigation and award of compensation.

Systemic methyl bromide (CH3Br) poisoning with signs and symptoms of varying severity developed in nine greenhouse workers after acute inhalational exposure on two consecutive days. Measurements of CH3Br, carried out at the site within hours after the accident, suggest that exposure on the second day may have been in excess of 200 ppm (800 mg/m3) CH3Br. All workers were admitted for observation. Seven of them were discharged after an uneventful overnight observation and residual symptoms, if any, subsided within three weeks of the accident. Two patients needed intensive care for several weeks because of severe reactive myoclonus and tonic-clonic generalised convulsions. These conditions were unresponsive to repeated doses of diazepam, clonazepam, and diphenylhydantoin but could be suppressed effectively by induction of a thiopental coma that had to be continued for three weeks. In some of the patients prior subchronic exposure to CH3Br, as shown by their occupational histories and high serum bromide (Br-) concentrations, is likely to have been a factor contributing to the severity of their symptoms. A direct association between serum Br- concentrations and the severity of neurological symptoms, however, seemed to be absent. An on site investigation into the circumstances leading to the accident showed the presence of an empty and out of use drainage system that covered both sections of the greenhouse. This was probably the most important factor contributing to the rapid and inadvertent spread of CH3Br.

The neuropathological findings in a man and his dog both of whom died after acute exposure to methyl bromide are presented. The dog had cerebral oedema, most marked in the depths of cortical sulci. The man survived 30 days after the initial illness and his brain contained well-defined symmetrical lesions in the mammillary bodies and inferior colliculi. He also had a peripheral neuropathy and lymphocytic thyroiditis. The pathology in the central nervous system has features resembling Wernicke's encephalopathology; the mechanism by which methyl bromide may produce such lesions is discussed.

The case reported in this issue of symmetrical brain stem damage associated with exposure to methylbromide has affinities with a number of analogous syndromes associated with tissue energy deprivation. Attention is drawn to topographical and metabolic similarities and differences in these conditions, and suggestions are made for possible ways of mitigating the damage in future cases that may also be of value in Wernicke and Leigh's diseases.

A case of preventable fatality and a nearly greater disaster as a result of methyl bromide fumigation of a restaurant is presented. Methyl bromide is a nearly odorless, volatile hydrocarbon used as a fumigant in the food industry. As a result of this episode, recommendations are made for worker and community notification of the hazards involved whenever fumigation takes place. Addition of a mucosal irritant or olfactory stimulant is recommended to provide warning for methyl bromide exposure.

A case of methyl bromide poisoning in a nurseryman is described. This case demonstrates the insidious nature and delayed action of the gas and the lengthy recovery period following poisoning and persistence of neurological signs and symptoms.

This work focuses on the neurophysiological features in a patient with action myoclonus and mental deterioration following methylbromide intoxication. The patient is a 28-year-old man, without respiratory distress or exposure to other toxics. Myoclonus improved with polytherapy (clonazepam, 5-HT, carbidopa, GABA). The neurophysiological and neuropsychological evidence in this patient suggests a possible double site of action of methylbromide at cortical and subcortical levels.

Symptoms as an important sign of the effects of methyl bromide were studied in 56 male workers (37 currently exposed and 19 previously exposed) in a methyl bromide factory. The workers were 18 to 62 yr of age (mean age: 41) and were exposed from 1 to 25 yr (mean: 7 yr). They were compared to 56 age-matched referents with a standardized questionnaire. The results of pairwise comparison of the symptoms of the age-matched pairs of exposed and referent subjects showed that the occurrence of dizziness, numbness, paresthesia and weakness of extremities, nightmares, fatigue and dry and scaly skin was statistically significantly higher among the workers than among the referents. When the symptoms during the work shift (acute symptoms) were compared, irritation symptoms such as itching, bullae or reddish swollen hands and runny noses with nasal irritation were reported significantly more often in the exposed groups. The correlation of the symptoms among the exposed workers suggested that chronic symptoms are closely related to acute irritation symptoms and exposure duration. The results suggest that symptom inquiry is useful for detecting the possible effects of exposure to methyl bromide.