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TIN COMPOUNDS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Inorganic tin compounds are divided into two series depending on the valence of tin; stannous compounds (tin (II)) and stannic compounds (tin (IV)). Examples of tin (II) compounds include stannous chloride (SnCl2), stannous oxide (SnO) and stannous flouride (SnF2). Stannic chloride (SnCl4) and stannic oxide (SnO2) are examples of tin (IV) compounds.

Specific Substances

    A) CONSTITUENTS OF THE GROUP
    1) Stannous compounds (Sn II)
    2) Stannic compounds (Sn IV)
    3) ORGANOTINS
    4) STANNIC COMPOUNDS
    5) STANNOUS COMPOUNDS
    6) TIN OXIDE (AS SN)
    7) TIN (SALTS)

Available Forms Sources

    A) FORMS
    1) Tin is a soft, colorless to silvery white solid found in crystal form (Lewis, 2000; Bingham et al, 2001). Inorganic tin compounds are divided into two series depending on the valence of tin; stannous compounds (tin (II)) and stannic compounds (tin (IV)). Examples of tin (II) compounds include stannous chloride (SnCl2), stannous oxide (SnO) and stannous flouride (SnF2). Stannic chloride (SnCl4) and stannic oxide (SnO2) are examples of tin (IV) compounds (Bingham et al, 2001).
    2) ORGANOTIN COMPOUNDS - Organotin compounds have at least one tin-carbon bond. Organotin compounds are toxic, with trimethyl and triethyl tins being the most toxic (Saary & House, 2002).
    B) SOURCES
    1) Tin is a naturally occurring metal in the earth's crust, but is also released in the environment due to mining, coal and oil combustion and production and use of tin products. Tin ore processing and smelting produces exposure to tin oxide, an inorganic tin compound.
    2) ORGANOTIN COMPOUNDS - Trimethyl tins are a byproduct of methyltin production (HSDB, 2003).
    3) TIN LEVELS IN CANNED FOODS AND BEVERAGES - In one study, it was determined that ingestion of canned food in which tin had leached form th cans with tin levels up to 267 mg/kg caused no adverse effects in healthy adults; this supports the currently proposed safe levels of tin for adults: 200 mg/kg and 250 mg/kg for canned beverages and canned foods, respectively (Boogaard et al, 2003). However, when tin(II) chloride was added to tomato juice, it caused irritant symptoms in 5.6% of subjects at a concentration of 161 mg/kg, 17% of subjects at 164 mg/kg, and 80% of subjects at 529 mg/kg. It appears that low molecular weight tin species and the complexes they form in food are responsible for the irritant effects.
    C) USES
    1) INORGANIC TIN COMPOUNDS
    a) Uses include food preservation, such as tin cans. Tin metal is used for plating steel and in the manufacture of solder and alloys such as bronze, brass, gun metal and pewter (Bingham et al, 2001). Tin readily joins with low temperature solders. It is alloyed with other metals to increase their hardness
    b) Tin is used in toothpaste to combat caries and in glass, soaps, perfumes, dyes and inks as a stabilizer.
    c) Inorganic tin salts are also used for various electrical, automobile and engineering parts.
    d) Stannous and stannic chlorides are used as pigments in ceramics and textiles.
    2) ORGANIC TIN COMPOUNDS
    a) ALKYLTIN: These compounds have been investigated as anthelmintic, fungicidal, and insecticidal agents. They have also been used as antioxidants or corrosion inhibitors, water-repellant coatings, thermal or electric coatings, and curing agents (HSDB, 2003).
    b) DIALKYLTINS: Higher alkyl compounds are used as stabilizers in plastics; others are fungicides.
    c) TRIALKYLTINS: The lower trialkyltins are powerful fungicides, molluscicides, insecticides, and miticides. Trialkyltin compounds are used primarily as biocides to preserve wood, paper, textiles, leather, and paints (HSDB, 2003).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Tin is a malleable, ductile and highly crystalline silvery-white metal. Organic tin compounds are used as wood preservatives, marine anti-fouling agents, as a biocide, and in the manufacture of polyvinyl chloride.
    B) TOXICOLOGY: There appears to be no serious risk from ingestion non-corrosive inorganic tin compounds. Organic tin compounds, however, may cause significant and varied toxicity. Organotin toxicity affects 4 main target organs: the brain, liver, immune system and the skin.
    C) EPIDEMIOLOGY: This is a very uncommon poison with only a handful of cases reported in the literature. Large overdoses produce mild to moderate symptoms with a few confirmed fatalities reported in the literature.
    D) WITH POISONING/EXPOSURE
    1) INORGANIC TINS: Inorganic tin compounds can cause nausea, vomiting, abdominal cramping, diarrhea, fatigue, and headache. Stannous oxide dust, when inhaled, can cause pneumoconiosis and occasionally bronchitis. Tin oxide fume inhalation can cause metal fume fever and pneumonitis. Stannic chloride, when mixed with water, releases fumes which may be corrosive and irritating to the eyes, mucous membranes, and skin.
    2) ORGANOTIN TOXICITY affects 4 main target organs: the brain, liver, immune system and the skin. The primary symptoms are skin and eye irritation, diarrhea, abdominal pain, and cholangeitis of the lower biliary tract with possible hepatotoxicity and neurotoxicity.
    3) MONOALKYL TINS have caused hepatomegaly, bile duct inflammation and necrosis, and renal fatty degeneration in animals.
    4) DIALKYL TINS: Ingestion has caused liver failure, peritonitis, and biliary tract damage in animals. Gastrointestinal hemorrhage may occur following oral exposure. Dialkyl tins are also local irritants which may produce skin lesions or eye irritation after a few minutes of contact.
    5) DIMETHYL TINS: Occupational exposure produced metabolic acidosis, acute renal failure, encephalopathy, elevated liver enzymes, and permanent neurologic deficits in one adult.
    6) TRIALKYL TINS: Effects include headache, nausea, visual defects, decreased hearing, tinnitus, paresthesias, EEG abnormalities, rarely respiratory failure, and possibly skin burns or dermatitis with dermal contact. Renal and hepatic toxicity have been reported in a few cases of triphenyltin acetate ingestion or dermal exposure.
    7) TETRAALKYL TINS: These are converted in the body to trialkyl tins, which may be toxic. Effects of exposure are, therefore, similar to those of the trialkyl tins, including headache, vomiting, tremors, hyperexcitability, muscle weakness and paralysis and possibly respiratory failure.
    8) TRIMETHYL TINS: Trimethyl tin chloride is generally well absorbed from the gastrointestinal tract and can be neurotoxic and may act as an acute excitotoxin at high levels. The primary neurological symptoms are headache, impaired memory, and behavioral changes such as aggressiveness, disorientation and psychotic behavior.
    0.2.20) REPRODUCTIVE
    A) Teratogenicity of tin and its compounds was not observed in animal studies.

Laboratory Monitoring

    A) Monitor hepatic and renal function after a significant or prolonged exposure as necessary.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Patients with a mild to moderate exposure are rarely symptomatic and require only supportive care.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Patients with severe toxicity, through dermal, inhalational, or oral exposure, usually have symptoms based on whether the tin is an inorganic or organic tin. INORGANIC TINS: Removal of any source is the first goal of management. Since inorganic tin compounds are rarely absorbed, supportive care for nausea, vomiting, abdominal cramping, diarrhea, fatigue, and headache are all that is usually indicated. Stannous oxide dust, when inhaled, can cause pneumoconiosis and occasionally bronchitis and tin oxide fume inhalation can cause metal-fume fever and pneumonitis. Consequently, patients who are exposed to these inorganic tins should have a detailed respiratory evaluation. Stannic chloride, when mixed with water, releases fumes which may be corrosive and irritating to the eyes, mucous membranes, and skin, removal of the fumes is usually the only treatment necessary. ORGANIC TINS: The 4 main target organs: the brain, liver, immune system and the skin. Removal of any source is the first goal of management. Patients who are exposed to organic tins are likely to complain of headache, vomiting, tremors, hyperexcitability, impaired memory, respiratory failure, skin burns, weakness and paralysis. While chelating agents, such as BAL have been tried in animals, adequate human data are not available. Aggressive supportive care is the mainstay of treatment. DERMAL EXPOSURE: Ideal decontaminate is soap and water. OCULAR EXPOSURE: Rinse with copious amounts of water or normal saline. INGESTION: Nausea and vomiting should be expected early in large tin ingestions. Supportive care is all that is required for inorganic tin ingestions as it is poorly absorbed. Organic tins will produce little gastrointestinal complaints. Symptoms of large acute ingestions to organic tin usually manifest over 2 to 4 days.
    C) DECONTAMINATION
    1) PREHOSPITAL: INGESTION: Generally, oral decontamination is not indicated. DILUTION: Immediately dilute with water after ingestion of a potentially corrosive tin compound (stannic chloride). Emesis is NOT indicated as certain organotins may be corrosive. DERMAL: Remove contaminated clothing; wash the exposed area with soap and water.
    2) HOSPITAL: INGESTION: Generally, oral decontamination is not indicated. DILUTION: Immediately dilute with water after ingestion of potentially corrosive tin compound (stannic chloride) and follow the treatment found in the ACIDS management. Of note, tin adds little to the toxicity. Emesis is NOT indicated as certain organotins may be corrosive. DERMAL: Remove contaminated clothing; wash the exposed area with soap and water.
    D) AIRWAY MANAGEMENT
    1) Organic tins cause respiratory depression through muscle paralysis. This is usually a late development that happens over 2 to 4 days. Pulmonary function testing should be used to monitor the patient's respiratory effort. Some of the inorganic tins might cause airway irritation; however, these rarely require airway management.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION
    1) There are no reports of a patient benefiting from enhanced elimination.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Asymptomatic patients can be managed at home. Any patient with vomiting or weakness should be evaluated at a healthcare facility.
    2) OBSERVATION CRITERIA: Patients with vomiting, headache, altered mental status, weakness or syncope should be evaluated at a healthcare facility and observed until signs and symptoms stabilize or improve.
    3) ADMISSION CRITERIA: Patients with a significant organotin exposure, (eg, large ingestion) should be admitted for cardiac, electrolyte, and respiratory monitoring.
    4) CONSULT CRITERIA: Consult a toxicologist or poison center for any patient with a significant exposure to organotins and fro a patient who develops respiratory failure, hemodynamic instability, or any other symptoms not expected with this exposure.
    H) PITFALLS
    1) Common errors for managing these patients include failing to screen for other exposures and not identifying other similar presenting medical conditions.
    I) DIFFERENTIAL DIAGNOSIS
    1) Patients with pneumoconiosis from metallic tin inhalation may be confused with those with other granulomatous lung diseases, such as silicosis or histoplasmosis. Patients with severe neurotoxicity from organotins may resemble patients with severe organolead toxicity or severe degenerative neurologic disease, such as spongiform encephalopathy or Creutzfelt-Jakob.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) Tin salts may cause pulmonary irritation of several days duration.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) TOXICITY: A toxic dose has not been established. INORGANIC TIN: Tin and its inorganic compounds are relatively nontoxic. ORGANOTIN COMPOUNDS: In general, these agents can produce acute toxicity, especially trialkyl and tetraalkyl derivatives. TRIPHENYLTIN ACETATE: 260 mg/kg ORALLY caused death in an adult. TRIETHYLIN: The estimated toxic dose is 90 mg/day for 8 days. BEVERAGE/INGESTION: Gastrointestinal symptoms occurred in volunteers who ingested canned juice, which contained 1370 mg/L of tin. OCCUPATIONAL EXPOSURE: Acute occupational exposure to trimethyltin produced limbic system and cerebellar dysfunction, and hearing loss in 6 men; a worker died 13 days after exposure.

Clinical Effects

Summary Of Exposure

    A) USES: Tin is a malleable, ductile and highly crystalline silvery-white metal. Organic tin compounds are used as wood preservatives, marine anti-fouling agents, as a biocide, and in the manufacture of polyvinyl chloride.
    B) TOXICOLOGY: There appears to be no serious risk from ingestion non-corrosive inorganic tin compounds. Organic tin compounds, however, may cause significant and varied toxicity. Organotin toxicity affects 4 main target organs: the brain, liver, immune system and the skin.
    C) EPIDEMIOLOGY: This is a very uncommon poison with only a handful of cases reported in the literature. Large overdoses produce mild to moderate symptoms with a few confirmed fatalities reported in the literature.
    D) WITH POISONING/EXPOSURE
    1) INORGANIC TINS: Inorganic tin compounds can cause nausea, vomiting, abdominal cramping, diarrhea, fatigue, and headache. Stannous oxide dust, when inhaled, can cause pneumoconiosis and occasionally bronchitis. Tin oxide fume inhalation can cause metal fume fever and pneumonitis. Stannic chloride, when mixed with water, releases fumes which may be corrosive and irritating to the eyes, mucous membranes, and skin.
    2) ORGANOTIN TOXICITY affects 4 main target organs: the brain, liver, immune system and the skin. The primary symptoms are skin and eye irritation, diarrhea, abdominal pain, and cholangeitis of the lower biliary tract with possible hepatotoxicity and neurotoxicity.
    3) MONOALKYL TINS have caused hepatomegaly, bile duct inflammation and necrosis, and renal fatty degeneration in animals.
    4) DIALKYL TINS: Ingestion has caused liver failure, peritonitis, and biliary tract damage in animals. Gastrointestinal hemorrhage may occur following oral exposure. Dialkyl tins are also local irritants which may produce skin lesions or eye irritation after a few minutes of contact.
    5) DIMETHYL TINS: Occupational exposure produced metabolic acidosis, acute renal failure, encephalopathy, elevated liver enzymes, and permanent neurologic deficits in one adult.
    6) TRIALKYL TINS: Effects include headache, nausea, visual defects, decreased hearing, tinnitus, paresthesias, EEG abnormalities, rarely respiratory failure, and possibly skin burns or dermatitis with dermal contact. Renal and hepatic toxicity have been reported in a few cases of triphenyltin acetate ingestion or dermal exposure.
    7) TETRAALKYL TINS: These are converted in the body to trialkyl tins, which may be toxic. Effects of exposure are, therefore, similar to those of the trialkyl tins, including headache, vomiting, tremors, hyperexcitability, muscle weakness and paralysis and possibly respiratory failure.
    8) TRIMETHYL TINS: Trimethyl tin chloride is generally well absorbed from the gastrointestinal tract and can be neurotoxic and may act as an acute excitotoxin at high levels. The primary neurological symptoms are headache, impaired memory, and behavioral changes such as aggressiveness, disorientation and psychotic behavior.

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) BLURRED VISION: Onset of blurred vision occurred 24 hours after ingestion of triphenyltin in an adult (Wu et al, 1990) and in 2 cases of triphenyltin acetate ingestion (Lin & Hsueh, 1993).
    2) NYSTAGMUS occurred following ingestion of triphenyltin (Wu et al, 1990; Lin et al, 1998).
    3) IRRITATION: The most toxic of dialkyl tins is diethyl tin which is a local irritant (Lyle, 1958) producing frequent skin lesions or eye irritation after only a few minutes of contact. This may manifest up to 1 to 8 hours after exposure, then rapidly resolve (Winship, 1988).
    a) Trialkyl tins may produce ocular irritation (Louria et al, 1972; Besser et al, 1987; Winship, 1988).
    b) The use of tributyltin-containing interior house paint was associated with eye irritation in the residents (Wax & Dockstader, 1995).
    3.4.4) EARS
    A) WITH POISONING/EXPOSURE
    1) TRIALKYL TIN produces decreased hearing and tinnitus (Louria et al, 1972; Besser et al, 1987; Winship, 1988).
    2) TRIMETHYLTIN and TRIETHYLTIN have produced structural and functional impairment of the auditory system in experimental animals; trimethyltin was more ototoxic than triethyltin in some studies (Clerici et al, 1991; Hoeffding & Fechter, 1991) (reviewed in Ryback, 1992).
    3.4.5) NOSE
    A) WITH POISONING/EXPOSURE
    1) IRRITATION: A burning sensation in the nasal mucosa and epistaxis were associated with an indoor exposure to paint containing bis(tributyltin) oxide in a woman and her two children (Anon, 1991). Nasal irritation was also reported in 5 members of a household exposed under similar circumstances (Wax & Dockstader, 1995).
    3.4.6) THROAT
    A) WITH POISONING/EXPOSURE
    1) Sore throat has been reported after the ingestion of triphenyltin acetate (Lin & Hsueh, 1993) and after inhalation of tributyltin-containing interior paint vapors (Wax & Dockstader, 1995).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) RESPIRATORY FINDING
    1) WITH POISONING/EXPOSURE
    a) Some organic tin compounds can cause respiratory tract irritation (ATSDR, 1992). Shortness of breath, coughing and wheezing have been reported from exposure to organic tin compounds (Louria et al, 1972; Besser et al, 1987; Winship, 1988), including exposure of household members to interior housepaint which contained bis(tributyltin) oxide (Anon, 1991; Wax & Dockstader, 1995).
    B) APNEA
    1) WITH POISONING/EXPOSURE
    a) Tetraalkyl tins are relatively inert, but are converted in the body to trialkyl tins, which are toxic. Its effects, therefore, mimic those of the trialkyl tins, which in severe exposure may result in respiratory failure due to weakness and/or paralysis of the respiratory muscles (Barnes & Stoner, 1959).
    C) METAL FEVER
    1) WITH POISONING/EXPOSURE
    a) Tin oxide fume inhalation has been reported to cause metal-fume fever and even fatal pneumonitis (Winship, 1988).
    D) PNEUMOCONIOSIS
    1) WITH POISONING/EXPOSURE
    a) CHRONIC EXPOSURE: Stannous oxide dust inhaled by miners and smelters results in a benign pneumoconiosis, called stannosis, and occasionally bronchitis. However, even after years of inhalational exposure and a tin dioxide lung content of 13 to 40%, no significant pathological response was noted to tin oxide dust (Robertson et al, 1961; Dundon & Hughes, 1950).
    E) ACUTE LUNG INJURY
    1) WITH POISONING/EXPOSURE
    a) TRIPHENYLTIN: In a clinical review of triphenyltin acetate exposures, 7 patients died following intentional oral exposure. Of those patients, 3 died of aspiration pneumonia with ARDS. The products contained 45% triphenyltin acetate, and ingestions ranged between 50 and 100 grams (Lin et al, 1998a).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ACUTE LUNG INJURY
    a) DIALKYL TIN when injected has caused pulmonary congestion and edema (Barnes & Stoner, 1958; Winship, 1988).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) NEUROTOXICITY
    1) WITH POISONING/EXPOSURE
    a) SUMMARY: Trimethyl tin can produce neurotoxicity following exposure and acts as an acute excitotoxin at high levels. It is able to cause neuronal necrosis by affecting neurons of the limbic system including the hippocampus and portions of the cortex (Saary & House, 2002).
    b) TRIMETHYL TIN: Early effects in a fatal acute exposure included tinnitus, lightheadedness, aggression, and unresponsiveness. Neuronal necrosis in specific areas of the brain was found to be associated with the exposure in this patient (Kreyberg et al, 1992).
    B) TOXIC ENCEPHALOPATHY
    1) WITH POISONING/EXPOSURE
    a) DIMETHYLTIN COMPOUNDS: A 43-year old man became disoriented with mental deterioration and developed leukoencephalopathy following occupational exposure to dimethyltin (DMT) over a 4-day period, despite protective clothing and an air supplied mask. Four days after exposure the patient was comatose with metabolic acidosis, severe hypokalemia (K+ 1.6 mmol/L), and evidence of acute renal failure. Rhabdomyolysis was present by day 7. The patient was started on British-anti-Lewisite (BAL) and he gradually became more alert. By day 20, the patient was responding to verbal commands, but neurologic deficits remained. A nerve conduction velocity study showed peroneal neuropathy of the axonal type. Upon discharge on day 163, the patient continued to have moderate ataxia, memory loss, disorientation, and speech difficulty (Yoo et al, 2007).
    b) TRIPHENYL TIN: Confusion progressing to unconsciousness began approximately 12 days after a 23-year-old man ingested a molluscicidal agent, triphenyl tin. He remained unconscious for about 1.5 months (Wu et al, 1990).
    C) CEREBRAL EDEMA
    1) WITH POISONING/EXPOSURE
    a) DIALKYL TIN: Oral diiododiethyl tin killed over 100 people in France in 1954. Headache, beginning 4 days after ingestion, preceded cerebral edema (Anon, 1958).
    D) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) TRIMETHYL TIN: Partial complex seizures have been reported in an individual following acute inhalational exposure to trimethyl tin (Feldman et al, 1993).
    E) AMNESIA
    1) WITH POISONING/EXPOSURE
    a) TRIALKYL TIN (GENERAL): Exposure has been associated with altered consciousness and EEG abnormalities (Louria et al, 1972; Besser et al, 1987; Winship, 1988).
    b) TRIMETHYL TIN: Memory defects, spatial disorientation, and delirium developed 72 hours after acute inhalation exposure to trimethyl tin. Memory defects, cognitive dysfunction, and dysphoria persisted for at least 4 years after the exposure. Anticonvulsant medication was required for partial complex seizures for at least 7 years (Feldman et al, 1993).
    c) TRIMETHYL TIN: Memory deficits, disorientation and EEG abnormalities were reported in an adult following inhalational and dermal exposure to trimethyltin. The patient gradually improved over several months after removal from the exposure (Yanofsky et al, 1991). In another case, a 27-year-old graduate student was exposed to trimethyl tin via inhalation and complained of difficulty with short-term memory (Saary & House, 2002).
    d) TRIPHENYLTIN ACETATE (TPTA): Neurological impairment which included: disorientation, involuntary movements of hands, facial twitching, giddiness, vertigo, and EEG abnormalities developed gradually in a woman following an intentional ingestion of approximately 1/3 of a 100 g pack of 45% TPTA (Lin et al, 1998a). Some symptoms (slow reaction, mild weakness, and intermittent brooding) remained for one year after the exposure.
    F) ELECTROENCEPHALOGRAM ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) EEG abnormalities have been associated with exposure to trialkyl tin, cutaneous and inhalational exposure to trimethyl tin (Yanofsky et al, 1991), and cutaneous exposure to triphenyl tin (Colosio et al, 1991), and ingestion of triphenyltin acetate (Lin & Hsueh, 1993; Lin et al, 1998a).
    G) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) ORGANOTINS
    1) Headache, with or without weakness and loss of appetite, have been associated with the inhalation of vapors from interior housepaint which contained bis(tributyltin) oxide (Anon, 1991; Wax & Dockstader, 1995). They have also been described with the ingestion of triphenyltin acetate (Lin & Hsueh, 1993).
    2) Tetraalkyl tins are relatively inert, but are converted in the body to trialkyl tins, which are toxic. The effects, therefore, mimic those of the trialkyl tins, including tremors and weakness (Barnes & Stoner, 1959).
    3) TRIMETHYL TIN: A 27-year-old graduate student was exposed to trimethyl tin via inhalation while working on a chemistry project and developed symptoms within 3 hours. Initial symptoms were feelings of agitation and later that evening awakening with a piercing right-sided temporal headache. All symptoms gradually improved and resolved within 5 days (Saary & House, 2002).
    b) INORGANIC TINS
    1) Symptoms from ingestion of inorganic tin in food may include fatigue and headache (Louria et al, 1972; Winship, 1988).
    H) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) TRIPHENYLTIN ACETATE: In a retrospective review of 148 cases of acute triphenyltin exposure (i.e., intentional oral exposure or occupational exposure), altered consciousness (10.1%) and dizziness (8.9%) were most commonly reported (Lin et al, 1998a).
    I) PARALYSIS
    1) WITH POISONING/EXPOSURE
    a) TETRA and TRIALKYL TIN: Tetraalkyl tins are relatively inert, but are converted in the body to trialkyl tins, which are toxic. Symptoms, therefore, may be similar to those of trialkyl tins, including muscle weakness or paralysis with possible respiratory failure (Barnes & Stoner, 1959).
    J) NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Delayed sensorimotor polyneuropathy due to axonal degeneration and demyelination developed in a 23-year-old man following ingestion of triphenyl tin (Wu et al, 1990).
    b) CASE REPORT: Mild prolonged distal latency and reduced nerve conduction velocities of the radial, median, ulnar, sural, peroneal and tibial nerves were reported in a 19-year-old woman 53 days after ingestion of triphenyl tin acetate (Lin et al, 1998a).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SEIZURES
    a) Trialkyl tin injections in animals have caused ataxia, unsteadiness, and paralysis as the brain appears to be the target organ. In animal studies, the characteristic lesion was an interstitial edema of the myelin surrounding neuronal axons, producing generalized weakness, paralysis, tremors, seizures, and death due to respiratory failure (Barnes & Stoner, 1959).
    b) Dietary trimethyltin resulted in aggressive behavior, tremors and seizures in rats exposed over 25 days. Extensive neuropathology was identified, including neuronal cell necrosis in the limbic system and Wallerian-type axonal degeneration (Allen et al, 1994).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL HEMORRHAGE
    1) WITH POISONING/EXPOSURE
    a) DIALKYL TINS: The most toxic of these compounds is diethyl tin, which acts as a local irritant to the GI tract (Lyle, 1958); gastrointestinal hemorrhage may, therefore, follow oral exposure.
    B) DRUG-INDUCED GASTROINTESTINAL DISTURBANCE
    1) WITH POISONING/EXPOSURE
    a) INORGANIC TIN: Abdominal pain, diarrhea, and vomiting have all been reported after ingestion of inorganic tin in food (Louria et al, 1972; Winship, 1988; Wu et al, 1990). Gastrointestinal hemorrhage can occur following ingestion.
    b) ORGANIC TINS: Nausea, diarrhea, and abdominal and epigastric pain can occur after exposure (i.e., inhalation, ingestion or dermal absorption) (Louria et al, 1972; Besser et al, 1987; Winship, 1988; Saary & House, 2002).
    1) Nausea, vomiting, and loss of appetite were associated with indoor exposure to paint containing bis(tributyltin) oxide (Anon, 1991; Wax & Dockstader, 1995).
    2) Dermal exposure and/or ingestion of triphenyltin acetate has resulted in nausea, vomiting and abdominal pain; effects were delayed 2 days after the inhalational exposure (Colosio et al, 1991; Lin & Hsueh, 1993).
    3) TRIPHENYL TIN: In a retrospective review of 148 cases of acute triphenyltin exposure (i.e., intentional oral or occupational exposure), nausea and vomiting (30.4%) were most commonly reported (Lin et al, 1998a).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) Elevated serum transaminase levels, mucoproteins and C-reactive protein, generalized hepatomegaly, and biopsy evidence of hepatic inflammation were associated with dermal exposure to triphenyltin acetate in one adult (Colosio et al, 1991). The case had a history of daily ethanol intake of 200 g, which may have contributed to some hepatic abnormalities.
    b) Transient, mildly elevated serum transaminase activities occurred in three following ingestion of triphenyltin acetate (Lin & Hsueh, 1993; Lin et al, 1998a). It has also been reported following occupational exposure to dimethyltin compounds (Yoo et al, 2007).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATIC FAILURE
    a) DIALKYL TINS: Dialkyl tins have caused liver failure, peritonitis, and biliary tract damage when taken orally by animals (Barnes & Stoner, 1958; Winship, 1988).
    2) HEPATOMEGALY
    a) TRIPHENYL TIN: Hepatomegaly which may persist for 2 years has been reported in animals (Verschuuren et al, 1970).
    b) MONOALKYL TINS: Monoalkyl tins have caused hepatomegaly, bile duct inflammation and necrosis.

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) DIMETHYL TIN COMPOUNDS: A 43-year-old man developed mental deterioration following occupational exposure to dimethyltin over a 4-day period. Four days after exposure, the patient had developed metabolic acidosis, severe hypokalemia (K+ 1.6 mmol/L), rhabdomyolysis, and acute renal failure (BUN 67.6 mg/dL, Cr 2.35 mg/dL). Laboratory findings gradually improved with supportive care and chelation therapy; however, the patient had permanent neurologic sequelae (Yoo et al, 2007).
    b) TRIPHENYL TIN ACETATE: Ingestion of 140 to 360 mg/kg resulted in acute renal failure in 3 adults (Lin & Hsueh, 1993). Onset of acute renal failure occurred within 2 to 10 days of ingestion and was more rapid with higher doses.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RENAL FAILURE
    a) DIALKYL TINS: Dialkyl tins have caused renal fatty degeneration when taken orally by animals (Barnes & Stoner, 1958; Winship, 1988).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) METABOLIC ACIDOSIS
    1) WITH POISONING/EXPOSURE
    a) DIMETHYLTIN COMPOUNDS: A 43-year-old man developed mental deterioration following occupational exposure to dimethyltin over a 4-day period. Four days after exposure, the patient had developed metabolic acidosis (pH 7.178, pO2 71.5 mmHg, pCO2 25.1 mmHg, HCO3 9.1 mmol/L SaO2 93.2%), severe hypokalemia (K+ 1.6 mmol/L), and acute renal failure. Laboratory findings gradually improved with supportive care and chelation therapy; however, the patient had permanent neurologic sequelae (Yoo et al, 2007).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) POISONING
    1) WITH POISONING/EXPOSURE
    a) Cutaneous exposure to triphenyl tin acetate resulted in systemic effects, suggesting that percutaneous absorption may occur (Colosio et al, 1991).
    B) SKIN IRRITATION
    1) WITH POISONING/EXPOSURE
    a) Stannic chloride, when mixed with water releases fumes, which may be corrosive and irritating to the skin.
    b) DIALKYL TINS: The most toxic of these compounds is diethyl tin which acts as a local irritant (Lyle, 1958). It produces frequent skin lesions after only a few minutes of contact. These may manifest up to 1 to 8 hours later, and then rapidly resolve thereafter (Winship, 1988).
    c) TRIALKYL TINS: Trialkyl tin may produce skin burns, erythema, or dermatitis (Louria et al, 1972; Besser et al, 1987; Winship, 1988).
    d) TRIBUTYL TIN: Tributyl tin has caused acute burns or subacute dermal irritation in humans (Klaassen et al, 1986; Grace et al, 1991).
    C) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) METALLIC TIN, TIN CHLORIDE: Caused contact sensitization in about 10% of nickel sensitive subjects (Menne et al, 1987). Positive patch test results to metallic tin and tin chloride have also been reported in persons who were not sensitive to nickel (de Fine Olivarius et al, 1993).
    D) ERUPTION
    1) WITH POISONING/EXPOSURE
    a) TRIPHENYL TIN ACETATE: An erythematous eruption covering the trunk occurred more than 24 hours after cutaneous exposure to triphenyltin acetate (Colosio et al, 1991). The individual had a prior history of exposure to this chemical without reaction. Patch testing was negative.
    b) TRIPHENYL TIN: In a retrospective review of 148 cases of acute triphenyl tin exposures (i.e., intentional oral or occupational exposure), skin burns (10.1%) and urticaria (8.9%) were commonly reported (Lin et al, 1998a).
    c) TRIBUTYLTIN OXIDE: Eczematous lesions, with erosions and blister formation were reported in a worker with tributyltin oxide exposure from contaminated work clothes. The substance could not be washed off the clothes after laundering (Grace et al, 1991).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) RHABDOMYOLYSIS
    1) WITH POISONING/EXPOSURE
    a) Rhabdomyolysis occurred in a 43-year-old man following a 4-day occupational exposure to dimethyltin compounds (Yoo et al, 2007).
    3.15.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) BONE DEVELOPMENT ABNORMAL
    a) RATS - Bone formation was decreased in rats fed stannous chloride.

Endocrine

    3.16.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ENDOCRINE DISORDER
    a) DIALKYL TINS have caused a reduction of thymus size and function when taken orally by animals (Barnes & Stoner, 1958; Winship, 1988).

Immunologic

    3.19.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IMMUNE SYSTEM DISORDER
    a) TRIPHENYL TIN is a potent immunosuppressant in animals (Verschuuren et al, 1970).

Reproductive

    3.20.1) SUMMARY
    A) Teratogenicity of tin and its compounds was not observed in animal studies.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) Teratogenicity of tin and its compounds was not observed in animal studies (Winship, 1988).
    2) One study found that di-n-butyltin diacetate, given orally to rats, induced clefting of lip, mandible and tongue and also increased resorption when given in a standard protocol regime (Schardein, 2000).
    3) In one animal study, delayed ossification of the fetal skeleton was noted after tributyltin chloride in utero exposure (10 mg/kg or 20 mg/kg). In addition, there was a significant increase in the incidence of low weight (less than or equal to 0.75 of the mean) fetuses after exposure to tributyltin chloride (20 mg/kg) (Adeeko et al, 2003).
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) In one animal study, Sprague-Dawley pregnant rats were gavaged with either vehicle (olive oil) or tributyltin chloride (0.25, 2.5, 10, or 20 mg/kg) from days 0 to 19 or 8 to 19 of gestation. After the highest doses of tributyltin chloride (20 mg/kg) were used, decreased litter sizes, a significant reduction in maternal weight gain and a significant increase in post-implantation loss were observed. When tributyltin chloride 10 or 20 mg/kg were used throughout gestation, serum thyroxine and triiodothyronine concentrations were reduced significantly in dams. Serum thyroxine concentrations (not triiodothyronine) were reduced significantly after the use of tributyltin chloride (2.5 and 10 mg/kg) from gestation days 8 to 19 days (Adeeko et al, 2003).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS7440-31-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) ANIMAL STUDIES
    a) Carcinogenicity of tin and its compounds was not observed in animal studies (Winship, 1988).

Genotoxicity

    A) Organic and inorganic tin compounds have produced genotoxic effects in numerous studies.

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) ANEMIA
    1) WITH POISONING/EXPOSURE
    a) Tin may interfere with essential metal absorption and metabolism thus inhibiting hematopoiesis and reducing hemoglobin concentrations (Winship, 1988).
    B) LEUKOPENIA
    1) WITH POISONING/EXPOSURE
    a) Mild anemia (hemoglobin 11.9 g/dL) and leukopenia (WBC 1860/mm3) developed in a 19-year-old woman after ingestion of triphenyltin acetate (Lin et al, 1998a).
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LEUKOPENIA
    a) Transient, progressive decrease in total leukocyte count occurred over 20 weeks of oral exposure of monkeys to bis (tri-n-butyltin) oxide. No other hematologic effects or toxicity were detected (Karrer et al, 1992).
    2) LACK OF EFFECT
    a) No abnormalities in enzyme activities involved in heme biosynthesis or in the concentration of free erythrocyte protoporphyrins and coproporphyrins were found in the blood of rabbits following oral administration of 2 mg tin (as stannous chloride) per kg for 5 days (Chmielnicka et al, 1993).
    3) ANEMIA
    a) Intraperitoneal administration of 17 mcg tin per kg (as stannous chloride) daily for several weeks produced significant decreases in hematocrit and hemoglobin, decreased erythrocyte count, and increased mean corpuscular volume and mean corpuscular hemoglobin in rabbits. Oral administration of 85 mcg tin (as stannous chloride) per kg also decreased hematocrit, hemoglobin and erythrocyte count after 6 to 10 weeks, but these normalized by 16 weeks (Chmielnicka et al, 1993).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor hepatic and renal function after a significant or prolonged exposure as necessary.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) If significant amounts of organotins have been ingested, hepatic and renal function should be monitored.
    a) BACKGROUND LEVELS: The average concentration of tin in blood of normal subjects is 0.14 mg/L, most of this resides in the erythrocytes and is thought to be due to daily diet. A typical diet contains 3.6 mg of tin, which is derived from canned foods (Baselt, 2000).
    4.1.3) URINE
    A) URINALYSIS
    1) Obtain a baseline urine level following a significant or prolonged exposure. NOTE: In the average American adult, urine tin concentrations have been estimated to average 0.023 mg/L, with a range of 0 to 0.04 mg/L (Baselt, 2000).
    4.1.4) OTHER
    A) OTHER
    1) TISSUE
    a) BACKGROUND LEVELS: Tin accumulates to a small extent in the body as aging occurs, and is randomly distributed. In American adults, lung, liver and kidney specimens usually contain from 0.2 to 1.2 mg/kg of tin (Winship, 1988; Baselt, 2000).

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) Tin can be quantified by emission spectroscopy, spark source spectrometry, neutron activation analysis (Versieck & Vanballenberghe, 1991), x-ray fluorescence, and atomic absorption spectroscopy.
    2) Inorganic tin can be determined in urine after extraction with hydrochloric acid and hexane-benzene, followed by pentylation and gas chromatography with flame photometric detection (Ohhira & Matsui, 1993).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with a significant organotin exposure, (eg, large ingestion) should be admitted for cardiac, electrolyte, and respiratory monitoring.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Asymptomatic patients can be managed at home. Any patient with vomiting or weakness should be evaluated at a healthcare facility.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a toxicologist or poison center for any patient with a significant exposure to organotins and for a patient who develops respiratory failure, hemodynamic instability, or any other symptoms not expected with this exposure.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with vomiting, headache, altered mental status, weakness or syncope should be evaluated at a healthcare facility and observed until signs and symptoms stabilize or improve.

Monitoring

    A) Monitor hepatic and renal function after a significant or prolonged exposure as necessary.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) EMESIS
    1) Inducing emesis is seldom necessary for patients who have ingested inorganic tin compounds, and may be dangerous in patients who have ingested certain organotins that may be corrosive.
    B) DILUTION
    1) Immediately dilute with water after ingestion of a potentially corrosive tin compound (stannic chloride).
    C) ACTIVATED CHARCOAL
    1) Should be avoided after ingestion of corrosive forms of tin due to the risk of causing vomiting, or of obscuring GI tract damage during endoscopy.
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS
    1) INORGANIC SALTS Inducing emesis is seldom necessary for patients who have ingested inorganic tin compounds due to their low systemic toxicity . Emesis is NOT indicated as certain ORGANOTINS may be corrosive (stannic chloride).
    B) DILUTION
    1) Immediately dilute with water after ingestion of potentially corrosive tin compound (stannic chloride) and follow the treatment found in the ACIDS management. Of note, tin adds little to the toxicity.
    2) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    C) ACTIVATED CHARCOAL
    1) Activated charcoal has not been tested with tin salts and these agents may be potentially irritating or corrosive.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY: Patients with mild to moderate exposure are rarely symptomatic and require only supportive care.
    2) MANAGEMENT OF SEVERE TOXICITY: Patients with severe toxicity, through dermal, inhalational, or oral exposure, usually have symptoms based on whether the tin is an inorganic or organic tin. INORGANIC TINS: Removal of any source is the first goal of management. Since inorganic tin compounds are rarely absorbed, supportive care for nausea, vomiting, abdominal cramping, diarrhea, fatigue, and headache are all that is usually indicated. Stannous oxide dust, when inhaled, can cause pneumoconiosis and occasionally bronchitis and tin oxide fume inhalation can cause metal-fume fever and pneumonitis. Consequently, patients who are exposed to these inorganic tins should have a detailed respiratory evaluation. Stannic chloride, when mixed with water, releases fumes which may be corrosive and irritating to the eyes, mucous membranes, and skin, removal of the fumes is usually the only treatment necessary. ORGANIC TINS: Removal of any source is the first goal of management. Patients who are exposed to organic tins are likely to complain of headache, vomiting, tremors, hyper excitability, impaired memory, respiratory failure skin burns, weakness and paralysis. The 4 main target organs: the brain, liver, immune system and the skin. While chelating agents, such as BAL have been tried in animals, adequate human data are not available. Aggressive supportive care is the mainstay of treatment.
    3) DERMAL EXPOSURE: Ideal decontaminate is soap and water.
    4) OCULAR EXPOSURE: Rinse with copious amounts of water or normal saline.
    5) INGESTION: Nausea and vomiting should be expected early in large tin ingestions. Supportive care is all that is required for inorganic tin ingestions as it is poorly absorbed. Organic tins will produce little gastrointestinal complaints. Symptoms of large acute ingestions to organic tin usually manifest over 20 to 4 days.
    B) CEREBRAL EDEMA
    1) CLINICAL IMPLICATIONS
    a) Cerebral edema and elevated intracranial pressure (ICP) may occur. Emergent management includes head elevation and administration of mannitol; hyperventilation should be performed if there is evidence of impending herniation.
    2) MONITORING
    a) Patients will usually require endotracheal intubation and mechanical ventilation. Monitor intracranial pressure, cerebral perfusion pressure and cerebral blood flow.
    3) TREATMENT
    a) Most information on the treatment of cerebral edema is derived from studies of traumatic brain injury.
    4) MANNITOL
    a) ADULT/PEDIATRIC DOSE: 0.25 to 1 gram/kilogram intravenously over 10 to 15 minutes (None Listed, 2000).
    b) AVAILABLE FORMS: Mannitol injection (5%, 10%, 15%, 20%, 25%).
    c) MAJOR ADVERSE REACTIONS: Congestive heart failure, hypernatremia, hyponatremia, hyperkalemia, renal failure, pulmonary edema, and allergic reactions.
    d) PRECAUTIONS: Contraindicated in well-established anuria or impaired renal function not responding to a test dose, pulmonary edema, CHF, severe dehydration; caution in progressive oliguria and azotemia. Do not add to whole blood for transfusions; enhanced neuromuscular blockade has occurred with tubocurarine. Keep serum osmolarity below 320 mOsm.
    e) MONITORING PARAMETERS: Renal function, urine output, fluid balance, serum potassium levels, serum osmolarity, and CVP.
    5) HYPERTONIC SALINE
    a) Preliminary studies suggest that hypertonic saline (7.5% saline/6% dextran) 100 ml reduced ICP more effectively than 200 mL of 20% mannitol in adults with elevated ICP after traumatic brain injury(Battison et al, 2005).
    6) ELEVATION
    a) Elevation of the head of the bed to approximately 30 degrees decreases ICP and improves cerebral perfusion pressure (Meixensberger et al, 1997; Schneider et al, 1993; Feldman et al, 1992).
    7) MECHANICAL DECOMPRESSION
    a) Early surgical decompression, ventriculostomy with CSF drainage, or craniectomy may be useful in patients with persistent elevation of ICP (Sahuquillo & Arikan, 2006; Sakai et al, 1998; Polin et al, 1997; Taylor et al, 2001). Most experience with these modalities has been in patients with traumatic brain injury.
    8) HYPERVENTILATION
    a) SUMMARY: Hyperventilation has been associated with adverse outcomes and should not be performed routinely (Muizelaar et al, 1991). It is indicated in patients who have clinical evidence of herniation or if there is intracranial hypertension refractory to sedation, paralysis, CSF drainage and osmotic diuretics (None Listed, 2000a).
    b) RECOMMENDATION:
    1) The PCO2 must be controlled in the range of 25 torr; further lowering of PCO2 may create undesirable effects secondary to local tissue hypoxia.
    2) End-tidal CO2 tension, correlated with an initial ABG measurement, provides a noninvasive means of monitoring PCO2 (Mackersie & Karagianes, 1990).
    3) Most authorities advise that hyperventilation should be considered a temporizing measure only; SUSTAINED hyperventilation should be avoided (Am Acad Neurol, 1997; Bullock et al, 1996; Kirkpatrick, 1997).
    C) DIMERCAPROL
    1) EXPERIMENTAL THERAPY
    a) SUMMARY
    1) BAL does not appear effective in removing tin compounds from the body; and therefore, should not be considered as an antidote
    2) (Shonwald, 2004).
    b) ANIMAL DATA
    1) Historically, BAL, a chelation therapy, had been used for tin toxicity in experimental animal studies. It was found to be an effective antidote against the general symptoms of dialkyltins, but did NOT prevent the biliary tract damage (Barnes & Stoner, 1958).
    2) However, in another study, BAL was NOT an effective antidote in experimental animals for trialkyltins, and therefore, should not be effective for tetralkyltins, which are converted to tialkyltins (Aldridge & Cremer, 1955).

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) IRRITATION SYMPTOM
    1) Inhalation of non-corrosive inorganic tin salts seldom causes acute toxicity. Benign pneumoconiosis may be a result of chronic inhalational exposure, but in and of itself does not necessitate specific treatment. Stannic chloride may release HCl fumes and cause acid-induced burns or irritation of the respiratory tract.
    2) ORGANOTIN SALTS
    a) May cause pulmonary irritation of several days duration. Remove patient from exposure and observe for pulmonary irritation or pulmonary edema.
    B) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).
    6.8.2) TREATMENT
    A) EYE IRRITATION
    1) Organotin salts (especially dialkyl or trialkyltin compounds or stannic chloride) may all produce eye irritation, photophobia, and visual disturbances.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) DERMATITIS
    1) Dibutyltins and tributyltins have caused cutaneous burns and dermatitis.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) SUMMARY
    1) There are no reports of a patient benefiting from enhanced elimination.

Abstracts

Case Reports

    A) LACK OF CLINICAL EFFECTS
    1) A man was employed for 26 years in a tin smelter exhibited profuse small radio-opaque nodules in the lungs, but was totally asymptomatic (Sluis-Cremer et al, 1989).
    B) CHRONIC EFFECTS
    1) A 55-year-old man who had worked for 15 years in a detinning plant had very profuse bilateral lung nodules each about 3 mm in diameter, and had a productive cough, basilar crackles, a forced vital capacity of 90%, and an FEV(1) of 96% of predicted values. A lung biopsy revealed blackish dust in some air spaces and also in the perivascular and peribronchiolar connective tissue; tin was shown to be present in the dust by electron microprobe analysis. However, he was also exposed to coal dust. (Sluis-Cremer et al, 1989).
    C) SPECIFIC AGENT
    1) TRIETHYLTIN: Contamination of a French antibacterial medication with triethyltin resulted in the poisoning of 217 individuals, 102 fatalities, and persistent symptoms for years in survivors (Barnes & Stoner, 1959).

Range Of Toxicity

Summary

    A) TOXICITY: A toxic dose has not been established. INORGANIC TIN: Tin and its inorganic compounds are relatively nontoxic. ORGANOTIN COMPOUNDS: In general, these agents can produce acute toxicity, especially trialkyl and tetraalkyl derivatives. TRIPHENYLTIN ACETATE: 260 mg/kg ORALLY caused death in an adult. TRIETHYLIN: The estimated toxic dose is 90 mg/day for 8 days. BEVERAGE/INGESTION: Gastrointestinal symptoms occurred in volunteers who ingested canned juice, which contained 1370 mg/L of tin. OCCUPATIONAL EXPOSURE: Acute occupational exposure to trimethyltin produced limbic system and cerebellar dysfunction, and hearing loss in 6 men; a worker died 13 days after exposure.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) NORMAL INTAKE - A typical dietary intake of tin is 3.6 milligrams daily, which is usually derived from canned foods (Baselt, 2000).

Minimum Lethal Exposure

    A) SUMMARY
    1) FATAL DOSE: 260 mg of triphenyltin acetate orally per kilogram of body weight was demonstrated to cause death in an adult (Lin & Hsueh, 1993).
    2) TRIETHYLTIN: In a clinical trial of 217 subjects conducted in the 1950's (Barnes & Stoner, 1959), a diethyltin compound was used to treat furunculosis. The compound was found to contain triethyltin as an impurity and 100 subjects died. The estimated toxic dose of triethyltin was 90 mg/day for 8 days. Symptoms of toxicity which began within 4 days, included persistent headache, vertigo, visual disturbances, abdominal pain, vomiting and psychiatric disturbances. Interstitial edema of the white matter of the brain was a characteristic finding at autopsy (Baselt, 2000).
    3) TRIMETHYLTIN: A urinary level of 1,580 ppb was reported in a fatal occupational exposure to trimethyltin in a 51-year-old man. The findings at autopsy included: tracheobronchitis, pneumonia, severe acute pulmonary edema, fatty degeneration of the liver, and renal injury (Besser et al, 1987).
    4) TRIPHENYLTIN: In a clinical review of triphenyltin acetate exposures, 7 patients died following intentional oral exposure. Of those patients, 3 died of aspiration pneumonia with ARDS. The products contained 45% triphenyltin acetate, and ingestions ranged between 50 and 100 grams (Lin et al, 1998a).

Maximum Tolerated Exposure

    A) SUMMARY
    1) Tin and inorganic tin compound exposures of approximately 500 mg/kg for 14 months was needed to produce toxicity (Klaassen et al, 1986).
    2) The toxicity of most organotins is not well documented. The estimated toxic dose of triethyltin is 90 mg/day for 8 days. Triethyltin is estimated to be 10 times as toxic as diethyltin orally (Barnes & Stoner, 1959).
    3) INGESTION: Gastrointestinal symptoms (nausea, vomiting and diarrhea) occurred in volunteers who ingested canned juice, which contained 1370 mg/L of tin. Subjects reported no effects after consuming juice which contained between 498 to 730 mg/L tin (Baselt, 2000).

Workplace Standards

    A) ACGIH TLV Values for CAS7440-31-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Tin, as Sn, oxide and inorganic compounds, except tin hydride
    a) TLV:
    1) TLV-TWA: 2 mg/m(3)
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Not Listed
    3) Definitions: Not Listed
    c) TLV Basis - Critical Effect(s): Pneumoconiosis; eye and URT irr; headache; nausea
    d) Molecular Weight: Varies
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:
    b) Adopted Value
    1) Tin, as Sn, organic compounds
    a) TLV:
    1) TLV-TWA: 0.1 mg/m(3)
    2) TLV-STEL: 0.2 mg/m(3)
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: A4
    2) Codes: Skin
    3) Definitions:
    a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    b) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.
    c) TLV Basis - Critical Effect(s):
    d) Molecular Weight: Varies
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:
    c) Adopted Value
    1) Tin, as Sn, metal
    a) TLV:
    1) TLV-TWA: 2 mg/m(3)
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Not Listed
    3) Definitions: Not Listed
    c) TLV Basis - Critical Effect(s):
    d) Molecular Weight: 118.69
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS7440-31-5 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Tin and inorganic compounds (as Sn)
    2) REL:
    a) TWA: 2 mg/m(3)
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s): [*Note: The REL also applies to other inorganic tin compounds (as Sn) except tin oxides.],
    3) Listed as: Tin (organic compounds, as Sn)
    4) REL:
    a) TWA: 0.1 mg/m(3)
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: [skin]
    1) Indicates the potential for dermal absorption; skin exposure should be prevented as necessary through the use of good work practices and gloves, coveralls, goggles, and other appropriate equipment.
    f) Note(s): [*Note: The REL applies to all organic tin compounds except Cyhexatin.]
    5) IDLH:
    a) IDLH: 100 mg Sn/m3
    b) Note(s): Not Listed
    6) IDLH:
    a) IDLH: 25 mg Sn/m3
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS7440-31-5 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Tin, as Sn, oxide and inorganic compounds, except tin hydride
    2) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Tin, as Sn, organic compounds
    a) A4 :Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
    3) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Tin, as Sn, metal
    4) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    5) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    6) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Tin and inorganic compounds (as Sn)
    7) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed ; Listed as: Tin (organic compounds, as Sn)
    8) MAK (DFG, 2002): Not Listed
    9) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS7440-31-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Tin, inorganic compounds (except oxides) (as Sn)
    2) Table Z-1 for Tin, inorganic compounds (except oxides) (as Sn):
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 2
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed
    3) Listed as: Tin, organic compounds (as Sn)
    4) Table Z-1 for Tin, organic compounds (as Sn):
    a) 8-hour TWA:
    1) ppm:
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 0.1
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) DICHLORO DIBUTYL TIN
    1) LD50- (ORAL)MOUSE:
    a) 70 mg/kg (RTECS, 2002)
    2) LD50- (ORAL)RAT:
    a) 50 mg/kg (RTECS, 2002)
    B) DICHLORO DIETHYL TIN
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 19 mg/kg (RTECS, 2002)
    2) LD50- (ORAL)MOUSE:
    a) 214 mg/kg (RTECS, 2002)
    3) LD50- (INTRAPERITONEAL)RAT:
    a) 20600 mcg/kg (RTECS, 2002)
    4) LD50- (ORAL)RAT:
    a) 509 mg/kg (RTECS, 2002)
    C) DICHLORO DIMETHYL TIN
    1) LD50- (ORAL)RAT:
    a) 73900 mcg/kg (RTECS, 2002)
    D) STANNOUS CHLORIDE
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 65598 mcg/kg (RTECS, 2002)
    2) LD50- (ORAL)MOUSE:
    a) 250 mcg/kg (RTECS, 2002)
    3) LD50- (INTRAPERITONEAL)RAT:
    a) 316 mg/kg (RTECS, 2002)
    4) LD50- (ORAL)RAT:
    a) 700 mg/kg (RTECS, 2002)
    E) TRIETHYL TIN SULFATE
    F) TRIMETHYL TIN CHLORIDE
    1) LD50- (INTRAPERITONEAL)RAT:
    a) 7450 mcg/kg (RTECS, 2002)
    2) LD50- (ORAL)RAT:
    a) 12600 mcg/kg (RTECS, 2002)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Tin is considered a nonessential element (Winship, 1988).
    B) Although once thought to be antibacterial, there is no evidence that tin has this effect. While various organotin compounds have some anthelmintic action, there is great variability in efficacy based on species of parasite (Barnes & Stoner, 1959).

Toxicologic Mechanism

    A) ALPHA KETOACID OXIDASE INHIBITION - The primary effect of dialkyltins is the inhibition of alpha ketoacid oxidases. This decreases oxygen utilization in the mitochondria, thus increasing pyruvate and lactate due to anaerobic metabolism. The effects are similar to phenylarsenious acid (Barnes & Stoner, 1959).
    B) INHIBITION OF OXIDATIVE PHOSPHORYLATION - Triethyltin appears to inhibit oxidative phosphorylation (Aldridge, 1958). It is a neurotoxin that produces a pathological effect which causes brain and spinal cord edema (Aschner & Aschner, 1992).
    C) TRIMETHYLTIN NEUROTOXICITY -
    1) Trimethyltin is primarily a CNS neurotoxin affecting neurons within the hippocampal pyramidal band and the fascia dentata (Aschner & Aschner, 1992). It may cause central neurotoxic effects via neuronal cell lesions in the limbic system, as has been shown in mice and rats (Chang, 1986; Allen et al, 1994). Alterations in ion balance of the neurons, or alteration of the cell membrane ATPase system have been proposed as contributing mechanisms in the neurotoxicity of this compound (Chang, 1986).
    2) Peripheral neurotoxicity may be due to neuronal cell lesions, degeneration of ventral horn cells in the spinal cord, and Wallerian-type axonal degeneration in peripheral nerve cells (Allen et al, 1994).
    3) Stannin, a 10 kDa peptide found in trimethyltin-sensitive cells, may play a role in the predisposition of certain cells to trimethyltin-induced toxicity (Toggas et al, 1992).

References

General Bibliography

    1) 40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.
    2) 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
    3) 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
    4) 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
    5) 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    6) 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    7) 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
    8) 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
    9) 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
    10) 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
    11) 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
    12) AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.
    13) Adeeko A, Li D, Forsyth DS, et al: Effects of in Utero tributyltin chloride exposure in the rat on pregnancy outcome. Toxicol Sci 2003; 74:407-415.
    14) Aldridge WN & Cremer JE: The biochemistry of organotin compounds-diethyltin dichloride and triethyltin sulphate. Biochem J 1955; 61:406-418.
    15) Aldridge WN: The biochemistry of organotin compounds. Trialkyltins and oxidative phosphorylation. Biochem J 1958; 69:367-376.
    16) Allen SL, Simpson MG, & Stonard MD: Induction of trimethyltin neurotoxicity by dietary administration. Neurotoxicology 1994; 15:651-654.
    17) Am Acad Neurol: Practice parameter: The management of concussion in sports (summary statement). Report of the Quality Standards Subcommittee. Neurology 1997; 48:581-585.
    18) American Conference of Governmental Industrial Hygienists : ACGIH 2010 Threshold Limit Values (TLVs(R)) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs(R)), American Conference of Governmental Industrial Hygienists, Cincinnati, OH, 2010.
    19) Anon: "Stalinon": a therapeutic disaster. Br Med J 1958; 1:515.
    20) Anon: Acute effect of indoor exposure to paint containing bis(tributyltin) oxide - Wisconsin, 1991. MMWR 1991; 40:280-281.
    21) Artigas A, Bernard GR, Carlet J, et al: The American-European consensus conference on ARDS, part 2: ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling.. Am J Respir Crit Care Med 1998; 157:1332-1347.
    22) Aschner M & Aschner JL: Cellular and molecular effects of trimethyltin and triethyltin: Relevance to organotin neurotoxicity. Neurosci Biobehavioral Rev 1992; 16:427-435.
    23) Barnes JM & Stoner HB: The toxicology of tin compounds. Pharmacol Rev 1959; 11:211-231.
    24) Barnes JM & Stoner HB: Toxic properties of some dialkyl and trialkyl tin salts. Br J Indust Med 1958; 15:15-22.
    25) Baselt RC: Disposition of Toxic Drugs and Chemicals in Man, 5th ed, Chemical Toxicology Institute, Foster City, CA, 2000.
    26) Battison C, Andrews PJ, Graham C, et al: Randomized, controlled trial on the effect of a 20% mannitol solution and a 7.5% saline/6% dextran solution on increased intracranial pressure after brain injury. Crit Care Med 2005; 33(1):196-202.
    27) Besser R, Kramer G, & Thumler R: Acute trimethyltin limbic-cerebellar syndrome. Neurol 1987; 37:945-950.
    28) Bingham E, Chorssen B, & Powell CH: Patty's Toxicology, Vol. 2, 5th ed, John Wiley & Sons, New York, NY, 2001.
    29) Boogaard PJ, Boisset M, Blunden S, et al: Comparative assessment of gastrointestinal irritant potency in man of tin(II) chloride and tin migrated from packaging . Food Chem Toxicol 2003; 41:1663-1670.
    30) Brower RG, Matthay AM, & Morris A: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Eng J Med 2000; 342:1301-1308.
    31) Bullock R, Chesnut RM, & Clifton G: Guidelines for the management of severe head injury. Eur J Emerg Med 1996; 2:109-127.
    32) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    33) Caravati EM: Alkali. In: Dart RC, ed. Medical Toxicology, Lippincott Williams & Wilkins, Philadelphia, PA, 2004.
    34) Cataletto M: Respiratory Distress Syndrome, Acute(ARDS). In: Domino FJ, ed. The 5-Minute Clinical Consult 2012, 20th ed. Lippincott Williams & Wilkins, Philadelphia, PA, 2012.
    35) Chang LW: Neuropathology of trimethyltin: a proposed pathogenetic mechanism. Fundam Appl Toxicol 1986; 6:217-232.
    36) Chiba M, Ogihara K, & Kikuchi M: Effect of tin on porphyrin biosynthesis. Arch Toxicol 1980; 45:189-195.
    37) Chmielnicka J, Zareba G, & Polkowska-Kulesza E: Comparison of tin and lead toxic action on etythropoietic system in blood and bone marrow of rabbits. Biol Trace Elem Res 1993; 36:73-87.
    38) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    39) Clerici WJ, Ross B Jr, & Fechter LD: Acute ototoxicity of trialkyltins in the guinea pig. Toxicol Appl Pharmacol 1991; 109:547-556.
    40) Colosio C, Tomasini M, & Cairoli S: Occupational triphenyltin acetate poisoning: a case report. Br J Industr Med 1991; 48:136-139.
    41) Cremer JE: The biochemistry of organotin compounds. The conversion of tetraethyltin into triethyltin in mammals. Biochem J 1958; 68:685-692.
    42) DFG: List of MAK and BAT Values 2002, Report No. 38, Deutsche Forschungsgemeinschaft, Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Wiley-VCH, Weinheim, Federal Republic of Germany, 2002.
    43) Datta NC: Metallic contamination of food stuffs Part III. Ind J Med Res 1940; 28:451-461.
    44) Dundon CC & Hughes JP: Stannic oxide pneumonconiosis. Am J Roent 1950; 63:797-812.
    45) EPA: Search results for Toxic Substances Control Act (TSCA) Inventory Chemicals. US Environmental Protection Agency, Substance Registry System, U.S. EPA's Office of Pollution Prevention and Toxics. Washington, DC. 2005. Available from URL: http://www.epa.gov/srs/.
    46) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    47) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    48) Feldman RG, White RF, & Eriator II: Trimethyltin encephalopathy. Arch Neurol 1993; 50:1320-1324.
    49) Feldman Z, Kanter MJ, & Robertson CS: Effect of head elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients. J Neurosurg 1992; 76:207-211.
    50) Ganguly BB: Bone marrow clastogenicity of trimethyltin. Mutat Res 1994; 312:9-15.
    51) Ghosh BB, Talukder G, & Sharma A: Frequency of chromosome aberrations induced by trimethyltin chloride in human peripheral blood lymphocytes in vitro: related to age of donors. Mech Ageing Dev 1991; 57:125-137.
    52) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    53) Grace CT, Ng SK, & Cheong LL: Recurrent irritant contact dermatitis due to tributyltin oxide on work clothes. Contact Dermatitis 1991; 25:250-271.
    54) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    55) HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 2003; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    56) Haas CF: Mechanical ventilation with lung protective strategies: what works?. Crit Care Clin 2011; 27(3):469-486.
    57) Hamasaki T, Sato T, & Nagase H: The genotoxicity of organotin compounds in SOS chromotest and rec-assay. Mutat Res 1992; 280:195-203.
    58) Hamasaki T, Sato T, & Nagase H: The mutagenicity of organotin compounds as environmental pollutants. Mutat Res 1993; 300:265-271.
    59) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    60) Hiles RA: Absorption, distribution and excretion of inorganic tin in rats. Toxicol Appl Pharmacol 1974; 27:366-379.
    61) Hoeffding V & Fechter LD: Trimethyltin disrupts auditory function and cochlear morphology in pigmented rats. Neurotoxicol Teratol 1991; 13:135-145.
    62) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide), 97, International Agency for Research on Cancer, Lyon, France, 2008.
    63) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol, 88, International Agency for Research on Cancer, Lyon, France, 2006.
    64) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Household Use of Solid Fuels and High-temperature Frying, 95, International Agency for Research on Cancer, Lyon, France, 2010a.
    65) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines, 89, International Agency for Research on Cancer, Lyon, France, 2007.
    66) IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures, 92, International Agency for Research on Cancer, Lyon, France, 2010.
    67) IARC: List of all agents, mixtures and exposures evaluated to date - IARC Monographs: Overall Evaluations of Carcinogenicity to Humans, Volumes 1-88, 1972-PRESENT. World Health Organization, International Agency for Research on Cancer. Lyon, FranceAvailable from URL: http://monographs.iarc.fr/monoeval/crthall.html. As accessed Oct 07, 2004.
    68) International Agency for Research on Cancer (IARC): IARC monographs on the evaluation of carcinogenic risks to humans: list of classifications, volumes 1-116. International Agency for Research on Cancer (IARC). Lyon, France. 2016. Available from URL: http://monographs.iarc.fr/ENG/Classification/latest_classif.php. As accessed 2016-08-24.
    69) International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. World Health Organization. Geneva, Switzerland. 2015. Available from URL: http://monographs.iarc.fr/ENG/Classification/. As accessed 2015-08-06.
    70) Karrer D, Baroncelli S, & Ciaralli L: Effect of subchronic bis(tri-n-butyltin)oxide (TBTO) oral administration on haematological parameters in monkeys: a preliminary report. Food Chem Toxicol 1992; 30:715-718.
    71) Kirkpatrick PJ: On guidelines for the management of the severe head injury (editorial). J Neurol Neurosurg Psychiatr 1997; 62:109-111.
    72) Klaassen CD, Amdur MD, & Doull J: Casarett and Doull's Toxicology: The Basic Science of Poisons, 3rd ed, Macmillan Publishing Co Inc, New York, 1986.
    73) Kollef MH & Schuster DP: The acute respiratory distress syndrome. N Engl J Med 1995; 332:27-37.
    74) Lewis RJ: Sax's Dangerous Properties of Industrial Materials, 10th ed, John Wiley & Sons, New York, NY, 2000.
    75) Lin JL & Hsueh S: Acute nephropathy of organotin compounds. Am J Nephrol 1993; 13:124-128.
    76) Lin T, Wu M, & Deng J: A retrospective study of 148 cases with acute triphenyltin acetate intoxication (abstract). J Toxicol Clin Toxicol 1998a; 36:466-467.
    77) Lin TJ, Hung DZ, & Kao CH: Unique cerebral dysfunction following triphenyltin acetate poisoning. Hum Exp Toxicol 1998; 17(7):403-5.
    78) Lin TJ, Hung DZ, & Kao CH: Unique cerebral dysfunction following triphenyltin acetate poisoning. Human & Exp Toxicol 1998a; 17:403-405.
    79) Louria DB, Joselow MM, & Browder AA: The human toxicity of certain trace elements. Ann Intern Med 1972; 76:307-319.
    80) Lyle WH: Lesions of the skin in process workers caused by contact with butyl tin compounds. Br J Ind Med 1958; 15:193-196.
    81) Mackersie RC & Karagianes TG: Use of end-tidal carbon dioxide tension for monitoring induced hypocapnia in head-injured patients. Crit Care Med 1990; 18:764-765.
    82) McLean JR, Birnboim HC, & Pontefact R: The effect of tin chloride on the structure and function of DNA in human white cells. Chem Biol Interact 1983; 46:189-200.
    83) Meixensberger J, Baunach S, & Amschler J: Influence of body position on tissue-pO2, cerebral perfusion pressure and intracranial pressure in patients with acute brain injury. Neurol Res 1997; 19:249-253.
    84) Menne T, Andersen KE, & Kaaber K: Tin: an overlooked contact sensitizer?. Contact Derm 1987; 16:9-10.
    85) Muizelaar JP, Marmarou A, Ward JD, et al: Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial.. J Neurosurg 1991; 75:731-739.
    86) NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.
    87) NHLBI ARDS Network: Mechanical ventilation protocol summary. Massachusetts General Hospital. Boston, MA. 2008. Available from URL: http://www.ardsnet.org/system/files/6mlcardsmall_2008update_final_JULY2008.pdf. As accessed 2013-08-07.
    88) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 1, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2001.
    89) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 2, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2002.
    90) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 3, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2003.
    91) NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 4, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2004.
    92) Naradzay J & Barish RA: Approach to ophthalmologic emergencies. Med Clin North Am 2006; 90(2):305-328.
    93) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,3-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    94) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,4-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    95) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Butylene Oxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648083cdbb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    96) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Dibromoethane (Proposed). United States Environmental Protection Agency. Washington, DC. 2007g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802796db&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    97) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,3,5-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    98) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 2-Ethylhexyl Chloroformate (Proposed). United States Environmental Protection Agency. Washington, DC. 2007b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037904e&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    99) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Acrylonitrile (Proposed). United States Environmental Protection Agency. Washington, DC. 2007c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648028e6a3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    100) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Adamsite (Proposed). United States Environmental Protection Agency. Washington, DC. 2007h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    101) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Agent BZ (3-quinuclidinyl benzilate) (Proposed). United States Environmental Protection Agency. Washington, DC. 2007f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ad507&disposition=attachment&contentType=pdf. As accessed 2010-08-18.
    102) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Allyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039d9ee&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    103) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    104) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Arsenic Trioxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480220305&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    105) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Automotive Gasoline Unleaded (Proposed). United States Environmental Protection Agency. Washington, DC. 2009a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cc17&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    106) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Biphenyl (Proposed). United States Environmental Protection Agency. Washington, DC. 2005j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1b7&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    107) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bis-Chloromethyl Ether (BCME) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648022db11&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    108) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Boron Tribromide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae1d3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    109) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromine Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2007d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039732a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    110) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromoacetone (Proposed). United States Environmental Protection Agency. Washington, DC. 2008e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187bf&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    111) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Calcium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    112) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae328&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    113) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Sulfide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037ff26&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    114) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Chlorobenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803a52bb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    115) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Cyanogen (Proposed). United States Environmental Protection Agency. Washington, DC. 2008f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187fe&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    116) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Dimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbf3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    117) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Diphenylchloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    118) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091884e&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    119) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Phosphorodichloridate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480920347&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    120) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809203e7&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    121) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    122) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Germane (Proposed). United States Environmental Protection Agency. Washington, DC. 2008j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963906&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    123) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Hexafluoropropylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1f5&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    124) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ketene (Proposed). United States Environmental Protection Agency. Washington, DC. 2007. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ee7c&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    125) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    126) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    127) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Malathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2009k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809639df&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    128) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Mercury Vapor (Proposed). United States Environmental Protection Agency. Washington, DC. 2009b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a087&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    129) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Isothiocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a03&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    130) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a57&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    131) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl tertiary-butyl ether (Proposed). United States Environmental Protection Agency. Washington, DC. 2007a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802a4985&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    132) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methylchlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5f4&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    133) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    134) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c646&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    135) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN1 CAS Reg. No. 538-07-8) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    136) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN2 CAS Reg. No. 51-75-2) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    137) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN3 CAS Reg. No. 555-77-1) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    138) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Tetroxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091855b&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    139) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Trifluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e0c&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    140) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008o. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e32&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    141) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perchloryl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e268&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    142) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perfluoroisobutylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2009d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26a&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    143) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008p. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dd58&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    144) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2006d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020cc0c&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    145) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    146) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phorate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008q. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dcc8&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    147) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene (Draft-Revised). United States Environmental Protection Agency. Washington, DC. 2009e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a08a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    148) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene Oxime (Proposed). United States Environmental Protection Agency. Washington, DC. 2009f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26d&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    149) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    150) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    151) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Propargyl Alcohol (Proposed). United States Environmental Protection Agency. Washington, DC. 2006e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec91&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    152) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Selenium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec55&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    153) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Silane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d523&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    154) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.
    155) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    156) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Strontium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    157) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sulfuryl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec7a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    158) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tear Gas (Proposed). United States Environmental Protection Agency. Washington, DC. 2008s. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e551&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    159) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tellurium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e2a1&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    160) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tert-Octyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2008r. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5c7&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    161) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tetramethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-17.
    162) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    163) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7d608&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    164) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethylacetyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008t. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5cc&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    165) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Zinc Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    166) National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for n-Butyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064808f9591&disposition=attachment&contentType=pdf. As accessed 2010-08-12.
    167) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    168) National Institute for Occupational Safety and Health: NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Cincinnati, OH, 2007.
    169) National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.
    170) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.
    171) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.
    172) National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.
    173) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    174) None Listed: The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Hyperventilation. J Neurotrauma 2000a; 17(6-7):513-520.
    175) None Listed: The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Use of mannitol. J Neurotrauma 2000; 17(6-7):521-525.
    176) Ohhira A & Matsui H: Gas chromatographic determination of inorganic tin in rat urine after a single oral administration of stannous chloride and mono-, di-, and triphenyltin chloride. J Chromatogr 1993; 622:173-178.
    177) Peate WF: Work-related eye injuries and illnesses. Am Fam Physician 2007; 75(7):1017-1022.
    178) Polin RS, Shaffrey ME, & Bogaev CA: Decompressive bifrontal craniectomy in the treatment of severe refractory posttraumatic cerebral edema. Neurosurgery 1997; 41:84-92.
    179) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    180) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    181) Robertson AJ, Rivers D, & Nagelschmidt G: Stannosis: benign pneumoconiosis due to tin dioxide. Lancet 1961; 1:1089-1093.
    182) Saary MJ & House RA: Preventable exposure to trimethyl tin chloride: A case report. Occup Med 2002; 52:227-230.
    183) Sahuquillo J & Arikan F: Decompressive craniectomy for the treatment of refractory high intracranial pressure in traumatic brain injury. Cochrane Database Syst Rev 2006; 2006(1):CD003983-.
    184) Sakai K, Iwahashi K, & Terada K: Outcome after external decompression for massive cerebral infarction. Neurol Med Chir 1998; 38:131-136.
    185) Schardein JL: Chemically Induced Birth Defects, 3rd ed, Marcel Dekker Inc, New York, NY, 2000.
    186) Schneider GH, von Helden GH, & Franke R: Influence of body position on jugular venous oxygen saturation, intracranial pressure and cerebral perfusion pressure. Acta Neurochir 1993; 59(suppl):107-112.
    187) Shonwald S: Tin. In: Dart RC, Caravati EM, MGuigan MA, et al. Medical Toxicology, 3rd ed. Lippincott Wilimans & Wilkins, Philadelphia, PA, 2004.
    188) Sluis-Cremer GK, Thomas RG, & Goldstein B: Stannosis. A report of 2 cases. S Afr Med J 1989; 75:124-126.
    189) Stolbach A & Hoffman RS: Respiratory Principles. In: Nelson LS, Hoffman RS, Lewin NA, et al, eds. Goldfrank's Toxicologic Emergencies, 9th ed. McGraw Hill Medical, New York, NY, 2011.
    190) Stoner HB, Barnes JM, & Duff JI: Studies on the toxicity of alkyltin compounds. Br J Pharmacol 1955; 10:16-25.
    191) Taylor A, Butt W, & Rosenfeld J: A randomized trial of very early decompressive craniectomy in children with traumatic brain injury and sustained intracranial hypertension. Childs Nerv Syst 2001; 17:154-162.
    192) Toggas SM, Krady JK, & Billingsley ML: Molecular neurotoxicology of trimethyltin: identification of stannin, a novel protein expressed in trimethytin-sensitive cells. Mol Pharmacol 1992; 42:44-56.
    193) U.S. Department of Energy, Office of Emergency Management: Protective Action Criteria (PAC) with AEGLs, ERPGs, & TEELs: Rev. 26 for chemicals of concern. U.S. Department of Energy, Office of Emergency Management. Washington, DC. 2010. Available from URL: http://www.hss.doe.gov/HealthSafety/WSHP/Chem_Safety/teel.html. As accessed 2011-06-27.
    194) U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project : 11th Report on Carcinogens. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Washington, DC. 2005. Available from URL: http://ntp.niehs.nih.gov/INDEXA5E1.HTM?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932. As accessed 2011-06-27.
    195) U.S. Environmental Protection Agency: Discarded commercial chemical products, off-specification species, container residues, and spill residues thereof. Environmental Protection Agency's (EPA) Resource Conservation and Recovery Act (RCRA); List of hazardous substances and reportable quantities 2010b; 40CFR(261.33, e-f):77-.
    196) U.S. Environmental Protection Agency: Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency. Washington, DC. 2011. Available from URL: http://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showSubstanceList&list_type=date. As accessed 2011-06-21.
    197) U.S. Environmental Protection Agency: List of Radionuclides. U.S. Environmental Protection Agency. Washington, DC. 2010a. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    198) U.S. Environmental Protection Agency: List of hazardous substances and reportable quantities. U.S. Environmental Protection Agency. Washington, DC. 2010. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.
    199) U.S. Environmental Protection Agency: The list of extremely hazardous substances and their threshold planning quantities (CAS Number Order). U.S. Environmental Protection Agency. Washington, DC. 2010c. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-part355.pdf. As accessed 2011-06-17.
    200) U.S. Occupational Safety and Health Administration: Part 1910 - Occupational safety and health standards (continued) Occupational Safety, and Health Administration's (OSHA) list of highly hazardous chemicals, toxics and reactives. Subpart Z - toxic and hazardous substances. CFR 2010 2010; Vol6(SEC1910):7-.
    201) U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.
    202) United States Environmental Protection Agency Office of Pollution Prevention and Toxics: Acute Exposure Guideline Levels (AEGLs) for Vinyl Acetate (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6af&disposition=attachment&contentType=pdf. As accessed 2010-08-16.
    203) Verschuuren HG, Ruitenberg EJ, & Peetoom F: Influence of triphenyltin acetate on lymphatic tissue and immune responses in guinea pigs. Toxicol Appl Pharmacol 1970; 16:400-410.
    204) Versieck J & Vanballenberghe L: Determination of tin in human blood serum by radiochemical neutron activation analysis. Anal Chem 1991; 63:1143-1146.
    205) Wax PM & Dockstader L: Tributyltin use in interior paints: a continuing health hazard. Clin Toxicol 1995; 33:239-241.
    206) Willson DF, Truwit JD, Conaway MR, et al: The adult calfactant in acute respiratory distress syndrome (CARDS) trial. Chest 2015; 148(2):356-364.
    207) Wilson DF, Thomas NJ, Markovitz BP, et al: Effect of exogenous surfactant (calfactant) in pediatric acute lung injury. A randomized controlled trial. JAMA 2005; 293:470-476.
    208) Winship KA: Toxicity of tin and its compounds. Adverse Drug React Acute Poisoning Rev 1988; 1:19-38.
    209) Wu RM, Chang YC, & Chiu HC: Acute triphenyltin intoxication: a case report. J Neurol Neurosurg Psychiatry 1990; 53:356-357.
    210) Yamada H & Sasaki YF: Organotins are co-clastogens in a whole mammalian system. Mutat Res 1993; 301:195-200.
    211) Yanofsky NN, Nierenberg D, & Turco JH: Acute short-term memory loss from trimethyltin exposure. J Emerg Med 1991; 9:137-139.
    212) Yoo CI, Kim Y, Jeong KS, et al: A case of acute organotin poisoning. J Occup Health 2007; 49(4):305-310.
    213) Yu WJ, Lee BJ, Nam SY, et al: Spermatogenetic disorders in adult rats exposed to tributyltin chloride during puberty. J Vet Med Sci 2003; 65(12):1331-1335.
    214) de Fine Olivarius F, Balslev E, & Menne T: Skin reactivity to tin chloride and metallic tin. Contact Dermatitis 1993; 29:110-111.