Vikane Gas: Sulfuryl Fluoride - Coursework Example

Vikane Gas: Sulfuryl Fluoride Introduction Sulfuryl Flouride is sold commercially under its trademark Vikane by Dow Agrosciences Australia Ltd. It is an inorganic gas fumigant containing 99.8% sulfuryl fluoride, and has been registered in the United States for the last forty years as a pesticide against termites, wood boring beetles, rodents and numerous other destructive pests. Sulfuryl fluoride has been used post-harvest, and to fumigate “buildings, construction materials, furnishings, nonedible commodities, and vehicles including rail cars” (Zettler and Arthur 2000, p.580). The chemical effectively destroys insects at all the active stages of life, whereas it has to be administered in higher doses or for longer periods of exposure to kill insect eggs. It is a highly toxic gas, which acts as a central nervous system depressant; and high concentrations can lead to respiratory failure. The odorless, colorless gas has no warning characteristics (Kamrin 1997) hence it contains the irritant chloropicrin as a warning indicator. Thesis Statement: The purpose of this paper is to investigate the properties, functions, uses, toxic effects, and various other dimensions of Vikane Gas or Sulfuryl Fluoride. The detection methods and treatment for nerve gases will also be examined. Discussion Industrial Uses, Exposure Routes, Toxic Effects of Vikane Gas Significantly, sulfuryl fluoride is licensed for use in several countries, which is an important consideration in increasing the use of the fumigant in postharvest control technology. It is currently registered as a structural fumigant, “and may be effective as a general commodity disinfestation treatment and as a quarantine treatment” (Zettler and Arthur 2000, p.581). In food premises storing grains the fumigant is used carefully because of its toxicity. Further, it is used as a quarantine treatment for dried fruits and nuts where control of the tolerant egg stage need not be taken into consideration; as in destroying an infestation of C. pomonella on walnuts and A. transitella on almonds. Sulfuryl fluoride has the lowest boiling point of any fumigant, -55.20C, and hence is in the gaseous state under all practical fumigation conditions. The exposure routes are mainly through inhalation and through the skin. Vikane gas, a Restricted Use Pesticide is in a pressurized condition in a steel cylinder from which it is dispensed through a hose into the interior of the sealed structure. After the elapse of a period of time, when air levels of sulfuryl fluoride have lowered to 1 part per million (ppm) or less, the interior of the structure is aerated. The Hazard Evaluation Division (HED) has not estimated occupational risks arising from dermal exposures since its possibility is considered to be low (Memorandum 2004). For Inhalation Exposure, the No Observed Adverse Effect Levels (NOAEL) for use in short-, intermediate-, and long-term inhalation assessments are as follows: Short term exposures of 1 to 7 days is equal to 100 ppm (30 mg/ kg/ day); Intermediate-term of 7 days to several months is equal to 30 ppm (8.5 mg/ kg/ day); and Long-term exposures of several months to lifetime is 30 ppm (8.5 mg/ kg/ day). A human activity factor of 2.0 representing light activity was used for all durations in the process of evaluating occupational exposures. The Hazard Identification and Assessment Review Committee (HIARC) recommended for short- and intermediate-term exposures, target margins of exposure (MOE), for occupational risk assessments. “The American Conference of Governmental Industrial Hygienists (ACGIH) has a Threshold Limit Value (TLV) of 5 ppm as an 8-hour time weighted average for sulfuryl fluoride, and a 15-minute short-term exposure limit (STEL) of 10 ppm” states Memorandum (2004, p.39) of the U.S. Environmental Protection Agency. Toxic effects of Vikane gas have been reported in humans following inhalation exposure to sulfuryl fluoride. High concentrations inhaled during short-term exposure have resulted in “respiratory irritation, pulmonary edema, nausea, abdominal pain, central nervous system depression, and numbness in the extremities” (Memorandum 2004, p.10). Violation of label directions, and exposure to high concentrations of the fumigant by inhalation over several hours has resulted in death with plasma fluoride level of 0.5 mg/ L, which is ten times the normal level. Prolonged chronic inhalation through exposure to sulfuryl fluoride gas substantially higher than the threshold limit value of 5 ppm causes fluorosis in humans, because the chemical is converted to fluoride anion in the body. This causes adverse outcomes such as the binding of fluoride anion to bone and to teeth causes a mottling of the teeth. A freezing effect on the surface of the eye and the skin have also been found. 1. Absorption, Distribution, Biotransformation Pathway of Vikane Gas As a post-harvest and structural fumigant controlling a wide range of insect pests “sulfuryl fluoride penetrates the insect’s body through inhalation at actively respiring life stages or by diffusion into the eggs” (FAO/ WHO 2006). The toxicity of the fumigant is non-specific, disrupting the glycolysis and citric acid cycles, consequently depriving the insect of essential energy for survival. When sulfuryl fluoride enters the target organism, it is broken down to the insecticidal fluoride anion which inhibits the insect’s metabolism. In the case of mammals, the rate and extent of oral absorption is not significant; however, it is rapidly absorbed by inhalation through nose, and maximum concentrations are reached at the end of the four-hour period. The absorbed dose which manifests radioactivity in urine, faeces and tissues is considered to be 14% at 30 parts per million (ppm), and 11% of the dose enters the lungs at 300 ppm. No data is available on dermal absorption, since it is estimated to be unlikely (Tech Report 2007). Distribution occurs 7 days after exposure. Sulfate is widely and evenly distributed among the tissues, radioactivity is detected mainly in the tissues at the site of first exposure of the gas. Further, increased fluoride levels occur in blood and tissues. Highest concentrations 7 days (168 hours) after exposure are in lungs, kindney, spleen and nasal turbinates. According to Mendrala et al (2002), a comparison of evidence for plasma and erythrocytes indicates an association of sulfate with erythrocytes. Rate of excretion is high, and occurs primarily through the urine: over 80%. Sulfate radioactivity gets rapidly cleared from plasma and red blood corpuscles consequent to a 30 ppm exposure with initial half-life of 2.5 hours, and after 300 ppm exposure: 1 to 2.5 hours. Terminal half-life of radioactivity is 2.5 times longer in red blood corpuscles than in plasma. The metabolism of sulfuryl fluoride in the body includes initial hydrolysis to fluorosulfate leading to release of fluoride, followed by “further hydrolysis to sulfate and release of the remaining fluoride” (Tech Report 2007, p.8). The toxicologically significant compounds are sulfuryl fluoride and fluoride ion. Thus, there is no possibility of sulfuryl fluoride accumulating since it gets hydrolyzed to fluoride. Through repeated exposure, accumulation of fluoride takes place in teeth and bones. To explain the biotransformation pathway of sulfuryl fluoride, chemical analysis shows only two radiolabelled components: sulfate and fluorosulfate. Parent sulfuryl fluoride is absent because of its rapid removal from blood. Fluorosulfate is identified by nuclear magnetic resonance (NMR) spectroscopy. The amount of fluorosulfate is around twice that of sulfate at all times after exposure; exception is 15 minutes after the beginning of the exposure at 300 ppm, when the concentration of fluorosulfate is found to be 6.5 times higher, similarly 4 hours after the end of exposure, when only a small quantity of fluorosulfate is found (Samuels et al 2005). At all sample test times, the concentrations of sulfate and fluorosulfate are around three to five times higher after exposure at 300 ppm than after exposure at 30 ppm. Further, “the half-life for the elimination of fluorosulfate from whole blood is calculated to be 48 to 73 minutes, while the half-life for elimination of sulfate from whole blood is calculated to be 50 to 64 minutes” (Samuels et al 2005, p.456). Two radioactive peaks identified as sulfate and fluorosulfate are detected in the urine. Parent sulfuryl fluoride in urine is not analysed because it hydrolyses rapidly in aqeous solutions. The quantity of fluorosulfate eliminated in the urine is 3 to 3.5 times greater than the amount of sulfate. The amount of sulfate recovered in the urine is greater than that of fluorosulfate; 12 hours after exposure, the quantity of sulfate recovered in the urine is five to seven times more than that of fluorosulfate. In a study using radiolabelled sulfuryl fluoride, it is found with the help of high performance liquid chromatography/ radioactivity monitor (HPL/ RAM), that the total amount of sulfate plus fluorosulfate recovered in the urine compares correctly with the amount of sulfuryl fluoride in the urine plus rinse. Calculation of half-lives for the elimination of sulfate and fluorosulfate in urine is possible by converting urinary concentrations of sulfate and fluorosulfate to rate estimates, to correct for unequal collection intervals. Fluorosulfate is found to be eliminated slightly faster at both 30 parts per million (ppm) and 300 ppm. Similarly, significant results emerge from fluoride analysis of urine in test rats and and non-exposed control rats. Therefore, based on the identification of fluorosulfate and sulfate in the blood and urine, it is stated that “the likely metabolic pathway for sulfuryl fluoride is initial hydrolysis to fluorosulfate, with release of fluorid, followed by further hydrolysis to sulfate and release of the remaining fluoride” (Samuels et al 2005, p.460). 2. Regulatory Limits and Epidemiological Data Current United States Environmental Protection Agency (EPA 2005, p.17) “reference concentrations for inhalation exposure to sulfuryl fluoride” are given as follows. Short-term, 1-30 days’ exposure: 0.30 mg/ kg/ day (workers), 0.03 mg/ kg/ day (residents); Intermediate term, 1-6 months’ exposure: 0.085 mg/ kg/ day (workers), 0.0085 mg/ kg/ day (residents); and Long term exposure of greater than 6 months: 0.028 mg/ kg/ day (workers); 0.0028 mg/ kg/ day (residents). For fluoride, the U.S. Environmental Protection Agency prescribes “the maximum contaminant level goal (MCLG) and secondary maximum contaminant level (SMCL) at 4 mg/ L, respectively, in the drinking water. These are equivalent to 0.114 mg fluoride/ kg/ day and 0.2 mg fluoride/ kg/ day for adults (70 kg and 2 L water/day) and children (10 kg and 1 L water/ day), respectively” (EPA 2005, p.17). The Office of the Environmental Health Hazard Assessment established a public health goal (PHG) of 1ppm or 1mg/ L for protection from dental fluorosis in children; this is equal to 0.1 mg fluoride/ kg/ day for children (10 kg and 1 L water/ day) (EPA 2005). Epidemiological data related to the effects of Vikane gas are as follows: In humans, exposure to high concentrations of Vikane gas and acute inhalation led to “respiratory irritation, lung damage, central nervous system depression, and death” (Medical Toxicology Branch, EPA 2005, p.vii). Evidence from epidemiological studies reveal that fumigation workers using sulfuryl fluoride had adverse neurological outcomes, including reduced performance on cognitive tests, memory tests and impaired olfactory function. Similarly, sulfuryl fluoride is acutely toxic at high concentrations in experimental animals. Lethal concentrations (LC) of 50% in rats are 3020-3730 ppm for one-hour exposure, and 991-1500 ppm for four-hour exposure. The 4-hour LC in mice is greater than 400 to 660 ppm. At non-lethal concentrations, “neurotoxicity is observed in rats, mice, rabbits, and dogs” (Medical Toxicology Branch, EPA 2005, p.vii). Repeated exposure of experimental animals to inhalation of sulfuryl fluoride resulted in damage primarily to the brain, respiratory system, and teeth. The active metabolite in the toxicity of sulfuryl fluoride is fluoride. For up to two weeks of exposure, the clinical signs that manifested included tremors, lethargy, respiratory effects, incapacitation, tetany, and convulsions. After 2 weeks of exposure to sulfuryl fluoride, tissue damage in the kidneys occurred in rats, the brain was affected in rabbits and mice, and there was damage to the respiratory tract in rabbits and dogs. After 13 weeks of inhalation exposure, the brain was the primary target for sulfuryl fluoride toxicity in all species studied: rats, mice, rabbits and dogs. The most commonly occurring lesion was the formation of vacuoles in cerebral tissue. Other outcomes reported were “nasal tissue inflammation in rats and rabbits, kidney hyperplasia in rats, lung histiocytosis in rats, thyroid hypertrophy in mice, and fluorosis in rats” (Medical Toxicology Branch, EPA 2005, p.viii). 3.Use of Chemicals as Terrorist Weapons “Chemical agents are those chemical compounds synthesized artificially and include the many toxic chemicals that may be available to terrorists” (Veenema 2007, p.367). From chlorine gas to the potentially injurious nerve gases are included in this category. Chemical weapons make use of the toxic nature of selected substances to cause death or injury through the respiratory tract, the oral route or via the skin. For terrorists intent on causing large-scale death and destruction, chemical weapons if used effectively can cause enormous casualties and massive disruption to society. Further, they are novel agents with the fear of the unknown inherent in them, and suit the predominant goal of terrorists, which is to target mass psychology, causing fear and uncertainty. Further, producing chemical weapons of mass destruction can be learnt from widely available literature, and they are also available as commercial products such as fumigants: for example vikane gas or sulfuryl fluoride. Chemicals that are colorless, odorless, and can easily spread through the environment are not easily detected. Sulfuryl fluoride is a highly toxic chemical in gaseous form, and depending on the concentration and dosage, can lethal particularly when inhaled. Its impact on the respiratory tract and nervous system causes serious damage to the heart, lungs, brain and other vital organs. Hence, regulatory bodies such as the environmental protection agency place restrictions on its use and dosage, and its commercialization is limited by the need for licenses. Despite precautions, the sulfuryl fluoride can be misused by terrorist outfits as a weapon of mass destruction. 4.Use of Animal Studies for Dose-Response Observation A short term study for 66 days with rats was conducted. The animals were fed diets fumigated with sulfuryl fluoride. Growth was retarded corresponding to the doses administered, except for the group receiving the lowest dose of 19 ppm fluoride. There was no mortality reported. The No Observable Effect Level (NOEL) was 2.5 mg fluoride/ kg based on reduced body weight gain and evidence of fluorosis (APVMA 2007). A subchronic study conducted for 13 weeks, on beagle dogs’ inhalation of vikane gas, the No Observed Effect Concentrations (NOEC) was 100 ppm due to slightly reduced body weights and histopathological changes in the brain at 200 ppm. These consisted of “very slight, small, bilateral focal vacuolation and gliosis in the putamen region of two of eight dogs at 200 ppm” (APVMA 2007, pp.6-7). On day 19, the male dog showed evidence of transient tremors and tetany some time after exposure was over, but appeared normal at all other times. In a chronic/ carcinogenecity study, rats were exposed through inhalation and whole body exposure to targeted concentrations of sulfuryl fluoride for 6 hours per day, 5 days a week, for up to 2 years. The No Observed Effect Concentration (NOEC) was 20 ppm, based on a variety of outcomes including “mortality, low body weights, very slight vacuolation in the brain, kidney pathology with associated clinical chemical effects and effects on other tissues, and pulmonary changes suggestive of irritation at 80 ppm, approximately equivalent to 5.6 mg/ kg bw/d” (APVMA 2007, p.6). Even at the highest concentration of the fumigant, there was no evidence of carcinogenecity in either sex. A developmental study was undertaken on inseminated rabbits exposed to specific concentrations of sulfuryl fluoride: 0, 25, 75 and 225 ppm via inhalation for 6 hours per day on days 6 through 18 of gestation. Loss of body weight during gestation due to maternal toxicity was observed in the 225 ppm exposure group. “The incidence of resorptions was not significantly increased among rabbits in any exposure group indicating that sulfuryl fluoride was not embryolethal at exposure levels as high as 225 ppm” (APVMA 2007, p.7). Fetal malformation was not evident. The No Observed Effect Concentration (NOEC) for maternal and fetotoxicity was 75 ppm. In a neurotoxicity study, female rats were exposed to 1, 100 or 300 ppm sulfuryl fluoride for 6 hours per day, on consecutive days. The study aimed at evaluating the effects of short-term inhalation exposure to high levels of sulfuryl fluoride on the central nervous system. The 13-week neurotoxicity study highlighted the “most sensitive, critical neorological end-point, visual, auditory and somatosensory evoked potential, when trying to establish an acute NOEC for sulfuryl fluoride” (APVMA 2007, p.8). No adverse effects were produced at the highest concentration tested, of 300 ppm. As outlined above, the effect of sulfuryl flouride on humans were estimated through studies conducted on animals. Reproductive and developmental toxicity studies revealed reduced body weight of fetuses in rabbits and rats. There were no teratogenic effects malformation in fetuses or embryos of rats or rabbits exposed to sulfuryl fluoride during gestation. In rats, mice and dogs chronic exposure to the fumigant affected the brain and the respiratory tract, foremost. Similar to the occurrence in subchronic exposure, brain vacuoles were found in the cerebrum. In the respiratory tract, lesions were found in nasal tissues, trachea, larynx and lungs. Both rats and dogs were affected by dental fluorosis. Death occurred in rats exposed to sulfuryl fluoride due to progressive glomerulonephropathy. The fumigant is not considered carcinogenic, as it does not produce tumors in rats and mice after lifetime exposure to it. Similarly, sulfuryl fluoride does not impact genetic material (Medical Toxicology Branch, EPA 2005). 6. Detection Methods and Treatments for Nerve Gases Emergency teams associated with environmental protection are equipped with chemical detectors and monitoring kits to respond to the release of any chemicals or toxic materials in the environment. In hospital emergency departments lacking appropriate detection technology, “the signs and symptoms of the victims may be the only detection method available” (Veenema 2007, p.485). Nerve agents are the most deadly of chemical weapons, since they are highly lethal through any route of exposure. Because nerve gases are odorless and colorless, it is difficult to detect them in the environment. Victims of nerve agent exposure have a clinical presentation of gasping, miosis, copious secretions, heavy sweating, and generalized twitching. Depending on the concentration of the agent, the duration and route of exposure, the onset of symptoms may differ from muscle fasciculations to eventual paralysis. Treatment for overdosage of vikane gas includes thorough decontamination, and appropriate emergency measures once the path of exposure has been determined. For respiratory failure and compromised airways, immediate endotracheal intubation has to given, with positive pressure ventilation. Suctioning out bronchial secretions may need to be done. “Treatment includes prophylactic anticonvulsants to prevent seizures, oximes to reactivate the inhibited acetylcholinesterase and reverse paralysis, and anticholinergics to antagonise the muscarinic effects” (Veenema 2007, p.488). To decontaminate through inhalation, 100% humidified oxygen should be administered. The eyes should be irrigated with saline. For dermal treatment, the area should be washed with soap and water. Supportive therapy: for frostbite standard treatment may be used, 0.5 to 1 gram of calcium for treating hypocalcemia. Further, isotonic fluids need to be administered and the patient placed in Trendelenburg position for hypotension; dopamine or norepinephrine can be used for refractory hypotension; and benzodiazepines or barbiturates for seizure control (Leikin & Paloucek 2007). Conclusion This paper has highlighted the industrial uses, exposure routes, and toxic effects of Vikane gas. Its absorption, distribution, and biotransformation pathway, as well as new regulatory limits and epidemiological data have been examined. The use of chemicals as terrorist weapons, animal studies to understand dose responses, and detection methods as well as treatment for nerve gases have been investigated. Sulfuryl fluoride is found to be a highly toxic gas, which can severely impact the central nervous system, the respiratory system and other vital organs. Depending on the dosage and duration of exposure, the effects of sulfuryl flouride on humans may be mild, severe or fatal. Future research in this area should focus on developing a less toxic version of the fumigant on humans, but one that is more efficient for use as a pesticide, while covering a wider range of insect and rodent pests. References APVMA. (2007). Evaluation of the new active sulfuryl fluoride in the product Profume Gas Fumigant. Public Release Summary. Australian Pesticide and Veterinary Medicines Authority. Retrieved on 9th April, 2010 from: http://permits.nra.gov.au/registration/assessment/docs/prs_sulfuryl_fluoride.pdf EPA. (2005). Sulfuryl fluoride (Vikane): Risk characterization document. Volume I. Health Risk Assessment. Final Draft. Medical Toxicology Branch. 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Office of Chemical Safety. Health risk assessment: Technical report. Retrieved on 7th April, 2010 from: http://loveforlife.com.au/files/59952%20-%20Tox%20and%20OH%20and%20S%20report.pdf Veenema, T.G. (2007). Disaster nursing and emergency preparedness: For chemical, biological, and radiological terrorism and other hazards. Edition 2. New York: Springer Publications. Zettler, J.L. & Arthur, F.H. (2000). Chemical control of stored product insects with fumigants and residual treatments. Crop Protection, 19: pp.577-782. Read More