Stability of Diazepam Solution for Injection Following Long-Term Storage in an Ambient Temperature of the Mediterranean Climate.

PURPOSE: Diazepam is utilized as a convulsion antidote following nerve gas attacks. As an emergency medicine, it requires storage at ambient temperatures which often doesn't meet manufacturers' requirements, leading to an early invalidation of the product. Current work investigated this issue. METHODS: Long-term stability of diazepam ampoules for injection stored in an ambient temperature of the Mediterranean climate for ~10 years vs storage at room temperature was studied. RESULTS: Diazepam assay and pH remained within pharmacopeial specifications irrespective of storage conditions. A major degradation product 2-methylamino-5-chlorobenzophenone (MACB) showed a clear trend of accumulation as a function of storage time, exceeding the permitted limit at ~2 years, irrespective of storage conditions. A strong correlation between the discoloration of the solutions and the concentration of MACB was obtained. Intravenous administration of MACB to rats at doses ~2200-fold higher than permissible specification levels caused neither mortality nor any toxicological nor post-mortem findings. CONCLUSIONS: Regarding the parameters tested: diazepam assay, MACB assay, and pH, storing ampoules of diazepam solution for injection in field conditions of high temperatures of the Mediterranean climate did not cause accelerated degradation as compared to room temperature. These findings open an option for the usage of expired ampoules in special scenarios.

Methylene Blue Administration During and After Life-Threatening Intoxication by Hydrogen Sulfide: Efficacy Studies in Adult Sheep and Mechanisms of Action.

Exposure to toxic levels of hydrogen sulfide (H2S) produces an acute cardiac depression that can be rapidly fatal. We sought to characterize the time course of the cardiac effects produced by the toxicity of H2S in sheep, a human sized mammal, and to describe the in vivo and in vitro antidotal properties of methylene blue (MB), which has shown efficacy in sulfide intoxicated rats. Infusing NaHS (720 mg) in anesthetized adult sheep produced a rapid dilation of the left ventricular with a decrease in contractility, which was lethal within about 10 min by pulseless electrical activity. MB (7 mg/kg), administered during sulfide exposure, maintained cardiac contractility and allowed all of the treated animals to recover. At a dose of 350 mg NaHS, we were able to produce an intoxication, which led to a persistent decrease in ventricular function for at least 1 h in nontreated animals. Administration of MB, 3 or 30 min after the end of exposure, whereas all free H2S had already vanished, restored cardiac contractility and the pyruvate/lactate (P/L) ratio. We found that MB exerts its antidotal effects through at least 4 different mechanisms: (1) a direct oxidation of free sulfide; (2) an increase in the pool of "trapped" H2S in red cells; (3) a restoration of the mitochondrial substrate-level phosphorylation; and (4) a rescue of the mitochondrial electron chain. In conclusion, H2S intoxication produces acute and long persisting alteration in cardiac function in large mammals even after all free H2S has vanished. MB exerts its antidotal effects against life-threatening sulfide intoxication via multifarious properties, some of them unrelated to any direct interaction with free H2S.

Fatal chlorine gas exposure at a metal recycling facility: Case report.

At least four workers at a metal recycling facility were hospitalized and one died after exposure to chlorine gas when it was accidentally released from an intact, closed-valved cylinder being processed for scrap metal. This unintentional chlorine gas release marks at least the third such incident at a metal recycling facility in the United States since 2010. We describe the fatal case of the worker whose clinical course was consistent with acute respiratory distress syndrome (ARDS) following exposure to high concentrations of chlorine gas. This case report emphasizes the potential risk of chlorine gas exposure to metal recycling workers by accepting and processing intact, closed-valved containers. The metal recycling industry should take steps to increase awareness of this established risk to prevent future chlorine gas releases. Additionally, public health practitioners and clinicians should be aware that metal recycling workers are at risk for chlorine gas exposure.

Hydrogen sulfide gas poisoning in fish garbage room: A report of a fisherman.

We report the case of a fisherman who was exposed to high concentrations of hydrogen sulfide (H2S) gas from the fish garbage room. The patient survived and was discharged with full recovery from the hospital. H2S is a colourless, foul smelling and highly toxic gas next to carbon monoxide, which causes inhalation death. It is a by-product of various industrial processes particularly involves exposure from agriculture, petrochemical industry and organic matter decomposition from sewage processing. It is a by-product of H2S has been referred as the "knock down gas" because inhalation of high concentrations can cause immediate loss of consciousness and death. Although early use of amyl nitrate and hyperbaric oxygen shows some benefit in literature, supportive care remains the mainstay of treatment. Emergency physicians and pre-hospital care personnel are not very familiar with such exposure due to its rarity. This becomes more relevant in the developing world settings where there are rising concerns about the unsafe exposure to hazardous chemicals and its impact on human health. Emergency physicians working in Pakistan should be aware of this entity especially in regard to fishermen presenting to the Emergency Department with such a clinical presentation and its toxic manifestations. This incident also illustrates the need of enforcement of health and safety regulations in the fishing industry.

[The morphological diagnostics of the toxic effects of the smoking blends in the cases of fatal intoxication with pyrrolidinovalerophenone]. / Morfologicheskaia diagnostika toksicheskogo vozdeistviia kuritel'nykh smesei v sluchaiakh smertel'nykh otravlenii pirrolidinvalerofenonom.

The objective of the present study was the development of the morphological criteria for the diagnostics of fatal intoxication with the herbal smoking blends (spices) using the samples of the biological materials obtained from the victims of pyrrolidinovalerophenone poisoning. The samples were taken from 13 autopsied cadavers of 11 men and 2 women at the age from 26 to 39 years based at the Astrakhan Regional Bureau of Forensic Medical Expertise during the period from 21011 to 2015. The diagnosis of pyrrolidinvalerpphenon poisoning was verified to the letter. The materials obtained during the standard autopsy procedure were used for the forensic genetic studies in the combination with the mandatory routine forensic chemical investigations with the application of the gas chromatographic techniques. Polymorphism of the morphological picture was attributable to the differences in the chemical composition of the poisons and the combination of narcotic and alcoholic intoxication. The signs of chronic intoxication manifested themselves in the form of mixed gliosis and various lesions of brain neurons. The variety of clinical symptoms and the morphological picture of pyrrolidinovalerophenone poisoning are responsible for different forms of tanatogenesis which suggests the necessity of further research on the mechanisms underlying the toxic effects of herbal smoking blends.

Identifying and Tracking Gas Suicides in the U.S. Using the National Violent Death Reporting System, 2005-2012.

INTRODUCTION: Identifying the source and specific type of gas used in suicides is difficult using most data systems owing to limitations in ICD-10 coding. The National Violent Death Reporting System (NVDRS), with its rich collection of both coded and free-text variables, has the potential to overcome these limitations. This study used a multipronged approach to identify gas-specific suicides in NVDRS and to track the incidence of these suicides over time. METHODS: Using suicide cases from the 16 NVDRS states that participated throughout 2005-2012, free-text and code searches were conducted for four types of variables-incident narratives, coroner/medical examiner cause-of-death statements, cause-of-death codes, and substance names-to identify suicides by carbon monoxide, helium, hydrogen sulfide, and four other gases. All analyses were conducted in 2015. RESULTS: Approximately 4% (3,242 of 80,715) of suicides recorded in NVDRS over the study period were the result of gas inhalation. Of these, the majority (73%) were carbon monoxide suicides (almost exclusively from motor vehicle exhaust and charcoal burning). Other types of gas (most notably helium), once rare, are now more common: At the start of the study period non-carbon monoxide gas suicides represented 15% of all gas suicides; at the end of the study period, they represented 40%. CONCLUSIONS: Public health policies to reduce a suicidal person's access to more lethal suicide methods require a reliable source of surveillance data on specific methods used in suicide. Small changes to NVDRS could make it an efficient and nimble surveillance system for tracking these deaths.

[Chemicals as fire damaging factor].

The article provides an overview of published scientific data about toxic chemical compounds formed during thermal degradation of various materials. In case of fire the complex of physical and chemical factors affect the human, along with injuries, thermal burns of the skin and respiratory tract there is a lack of oxygen in the inspired air and the impact of thermal degradation products. The greatest number of deaths in.a fire due to the inhalation by the victims smoke and toxic gases. The impact of the combination of toxic substances leads to the development of various forms of toxic process. The main causes of poisoning at the fires due to the effects of toxic substances and substances which can cause structural and functional disorders of the respiratory organ. Intoxication manifestations by some of them appear already in the fire zone, in other cases, in cases of poisoning by the compounds of the slow motion, there is the latent period of of intoxication. Knowledge of the spectrum of toxic products thermal destruction on the human during the fire, it is necessary to develop approaches to improve medical care and creation of tools of medical protection.

[Case of dyspnea due to toilet cleaner containing nitric acid for household use].

A 40-year-old male tried to clean a urinal at his home storing 900 mL of a toilet cleaner containing 9.8% nitric acid to remove calcium deposit, and clean the toilet floor for twenty minutes. Immediately after using the cleaner, he experienced eye irritation. He washed out the toilet cleaner. However, he thereafter experienced dyspnea, a compressive sensation in his chest, and chest and back pain about 40 minutes after the cleaning the toilet. He monitored his symptoms overnight and found them to gradually improve. However, the symptoms still remained the next morning and therefore he came to our department on foot. He had no particular past or family history. On arrival, his physiological findings and chest computed tomography scan were negative for any abnormalities. His arterial blood gas analysis revealed a mild abnormality of oxygenation. Observation without any drugs revealed that a complete remission of his symptoms occurred after approximately 4 weeks. Based on the results of the experiments, contact with the mucosal membrane and nitric acid gas produced by any accidentally coexisting metals or contact with moisture, including nitric acid produced by a reaction between CaCO3 and cleaner, may have been the mechanism of occurrence for the symptoms observed in this case. This is the first reported case of nitric acid poisoning due to the use of a toilet cleanser intended for household use.

Evaluation of DNA damage in construction-site workers occupationally exposed to welding fumes and solvent-based paints in Turkey.

In this study, the comet assay was used to evaluate whether welding fume and solvent base paint exposure led to DNA damage in construction-site workers in Turkey. The workers (n = 52) were selected according to their exposure in the construction site and controls (n = 26) from the general population, with no history of occupational exposure. The alkaline comet assay, a standard method for assessing genotoxicity, has been applied in peripheral lymphocytes of all subjects. The mean percentages of DNA in tail (%DNA(T)) of each group were evaluated, including the comparisons between smokers in each different group and the duration of exposure. Significant increase in the mean %DNA(T) (p < 0.01) was observed in all exposed subjects (12.34 ± 2.05) when compared with controls (6.64 ± 1.43). Also %DNA(T) was significantly high (p < 0.01) in welders (13.59 ± 1.89) compared with painters (11.10 ± 1.35). There was a statistical meaningful difference in % DNA(T) between control and exposed smokers. Our findings indicate that exposure to welding fumes and paints induce genotoxic effect in peripheral lymphocytes, indicating a potential health risk for workers. Therefore, to ensure maximum occupational safety, biomonitoring is of great value for assessing the risk for construction workers.

Mass casualties from acute inhalation of chlorine gas.

OBJECTIVES: Chlorine gas is a potent pulmonary irritant that affects the mucous membranes and induces severe disturbances of pulmonary gas exchange within minutes of inhalation. The present study evaluated an extraordinary type of mass inhalational exposure. MATERIAL AND METHODS: Clinical reports of 25 soldiers who were admitted to the emergency department of Maresal Cakmak Military Hospital, Erzurum were retrospectively evaluated. All patients were exposed to chlorine gas as a result of mixing sodium hypochlorite with hydrochloric acid during cleaning activities. RESULTS: All patients were male and the mean age of patients was 22.04+/-2.98 years. The main symptoms were coughing and dyspnea in 18 patients (72%). Forced expiratory volume in 1 second (FEV1) and FEV1/forced volume capacity (FVC) ratio were found to be normal in all patients but FVC and peak expiratory flow (PEF) were below the normal range (80%) in 9 patients (36%). All patients received warmed humidified oxygen combined with nebulized salbutamol. Inhaled budesonide and nebulized sodium bicarbonate were ordered additionally for 19 patients (76%). Thirteen patients (52%) were discharged from the emergency department and 12 patients (48%) were hospitalized. No mortality was observed. CONCLUSION: Chlorine gas is a potent pulmonary irritant that causes acute damage in both the upper and lower respiratory tract. We suggest that inhaled steroids combined with nebulized sodium bicarbonate could be a safe and effective alternative for the treatment of symptomatic patients. Education of the public about the dangers of mixing of hypochlorite bleach with acidic cleaning agents is also very important.

Metal fume fever: a review of the literature and cases reported to the Louisiana Poison Control Center.

Metal fume fever (MFF) is an important occupational-related illness resulting from inhalation of volatile metal oxides, especially zinc, that are produced during welding or cutting of metal materials. Onset of MFF is rapid, occurring within a few hours after inhalation of the fumes. Symptoms include fever, chills, cough, dyspnea, headache, myalgia, and malaise. Symptoms are self-limiting and typically resolve within 24 hours with a subsequent short-lived tolerance to zinc oxide fumes that disappears after one to two days of avoidance. In this report, we present an overview of MFF's history, pathogenesis, clinical presentation, regulatory guidelines, and prevention recommendations. This review is followed by a description of MFF cases reported by the Louisiana Poison Control Center to the Louisiana Office of Public Health's Section of Environmental Epidemiology and Toxicology during a two-year period.

[Gas poisoning: respiratory irritants and axphyxiants]. / Otrovanja plinovima: respiracijski iritansi i asfiksansi.

Inhalation exposure to harmful substances in the working as well as in general environment may induce serious health effects. The severity of gas poisoning is determined primarily by its physical and chemical characteristics, and the level and duration of exposure. Toxic effects from gas inhalation involve simple asphyxia, respiratory irritation, systemic toxicity, and a combination of these mechanisms. This article describes the characteristics, types of exposure and health effects of most common irritant and asphyxiant gases, including carbon monoxide, hydrogen cyanide and ammonia.

[Household gas poisonings]. / Otrovanja plinovima u kucanstvu.

Exposure to toxic gases which can induce serious health effects, can occur in the working as well as in general environment, including home. The severity of gas poisoning is determined by its physical and chemical characteristics, intensity and duration of exposure, and concomitant diseases and injuries in the poisoned person. Manifestations of gas toxic action involve simple asphyxia, local irritation of respiratory mucosa, systemic toxicity, and a combination of these mechanisms. This article describes the characteristics, modes of exposure and health effects of most common gases causing poisoning at home. These include gas fuels, carbon monoxide, ammonia, chlorine, and fire gases such as nitrogen and sulphur oxides, hydrogen cyanide and phosgene. First aid as well as preventive measures to avoid exposure to toxic gases and prevent fire at home are also given. The Croatian Poison Control Centre gathered data on toxic gas exposures in households between November 2005 and July 2006. During this period 30 persons (3 % of the total number of cases) were exposed to toxic gases at home, including carbon monoxide, irritating vapours from cleaning agents and disinfectants, gas fuels, septic tank gases, tear-gas, and chlorofluorocarbons from refrigerators.

Toxicological aspects of fire.

Most fatalities from fires are not due to burns, but are a result of inhalation of toxic gases produced during combustion. Fire produces a complex toxic environment, involving flame, heat, oxygen depletion, smoke and toxic gases. As a wide variety of synthetic materials is used in buildings (insulation, furniture, carpeting, electric wiring covering, decorative items), the potential for poisoning from inhalation of products of combustion is continuously increasing. In the present review, the problems that are present in a fire event, the toxicology of the toxic substances and the specific chemical hazards to firefighters are described. Regulatory toxicology aspects are presented concerning the use of non-flammable building and furnishing materials to prevent fires and decrease of poisonings and deaths resulting from fires.