[Changes in mass spectrometry of proteins in patients with 1-bromopropane poisoning after treatment].

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.

Large-scale label-free proteomics analysis of occupational poisoned patients of 1-bromopropane, workers exposed to 1-bromopropane and healthy individuals.

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.

[A clinical study of serum protein markers in patients with 1-bromopropane 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.

[The research of proteome profiling change of 1-bromopropane poisoning cases].

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.

Health consequences of exposure to brominated flame retardants: a systematic review.

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.

Cases from NACCT acute and intensive care symposium: altered mental status, seizures, and rash in a fumigation company employee.

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.

Methyl bromide exposure and cancer risk in the Agricultural Health Study.

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.

Illness associated with exposure to methyl bromide-fumigated produce--California, 2010.

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.

Characterization of a fatal methyl bromide exposure by analysis of the water cooler.

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.

Methylbromide intoxication: a clinical case study.

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.

[Neurotoxicity of organic solvents--recent findings].

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.

Severe neurotoxicity associated with exposure to the solvent 1-bromopropane (n-propyl bromide).

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.

[Peripheral neuropathy induced by acute methyl bromide skin exposure: a case report]. / Neuropathie périphérique par intoxication aiguë au bromure de méthyle: à propos d'une observation.

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.