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ALIPHATIC THIOCYANATES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) The clinical experience with sodium/potassium thiocyanate has been with its use and its associated toxicity in the treatment of hypertension. Sodium/potassium thiocyanate is no longer used in clinical medicine, but thiocyanate toxicity may still occur in the setting of prolonged or high dose sodium nitroprusside infusions.
    B) Synthetic aliphatic thiocyanates (rhodanates) are used as contact insecticides. These agents are used in kerosene-based sprays and dusting powders, and are sometimes combined with rotenone, piperonyl butoxide, or pyrethrum.
    C) Some available commercial products are: Lethane 384, Lethane 60, and Thanite. Lethane 384 Special is a dilute mixture of Lethane 384 and Lethane 60, and was used in the past as a treatment for pediculosis capitus.
    D) This document will focus primarily on the clinical experience with human sodium/potassium thiocyanate (thiocyanate) and lethane toxicity.

Specific Substances

    A) LETHANE 384
    1) 2-(2-Butoxyethoxy)ethyl thiocyanate
    2) 2-(2-(Butoxy)ethoxy)ethyl thiocyanic acid ester
    3) Butoxyrhodanodiethyl ether
    4) beta-Butoxy-beta'-thiocyanodiethyl ether
    5) 2-Butoxy-2'-thiocyanodiethyl ether
    6) 1-Butoxy-2-(2-thiocyanoethoxy) ethane
    7) Butyl carbitol rhodanate
    8) Butyl carbitol thiocyanate
    9) Ethane, 1-butoxy-2-(2-thiocyanatoethoxy)-
    10) Ethanol, 2-(2-butoxyethoxy)-, thiocyanate
    11) Lethane
    12) Lethane 384
    13) Thiocyanic acid 2-(2-butoxyethoxy)ethyl ester
    14) CAS 112-56-1
    LETHANE 60
    1) Dodecanoic acid 2-thiocyanatoethyl ester
    2) Lauric acid 2-thiocyanatoethyl ester
    3) Thiocyanic acid, 2-hydroxyethyl ester, laurate
    4) 2-Thiocyanoethyl coconate
    5) 2-Thiocyanoethyl dodecanoate
    6) beta-Thiocyanoethyl laurate
    7) 2-Thiocyanoethyl laurate
    8) CAS 301-11-1
    THANITE
    1) Acetic acid, thiocyanato-, isobornyl ester
    2) Acetic acid, thiocyanato-, 1,7,7-trimethylbi-
    3) cyclo(2,2,1)hept-2-yl ester
    4) Exo-
    5) Bornate
    6) Cidalon
    7) Isoborneol, thiocyanatoacetate
    8) Isobornyl thiocyanatoacetate
    9) Isobornyl thiocyanoacetate
    10) Terpinyl thiocyanoacetate
    11) Thanisol
    12) Thanite
    13) Thiocyanatoacetic acid isobornyl ester
    14) CAS 115-31-1
    LETHANE SPECIAL
    1) CAS 63917-01-1
    GENERAL TERMS
    1) ALIPHATIC THIOCYANATE
    2) RHODANATES

Available Forms Sources

    A) FORMS
    1) The aliphatic thiocyanate insecticides are yellow to brown volatile oily liquids that should float on water (Gosselin et al, 1984; Sax, 1982; Hayes, 1982; Lewis, 1996).
    B) SOURCES
    1) Available commercial products are: Lethane 384, Lethane 60, and Thanite (Gosselin et al, 1984). Lethane 384 Special is a dilute mixture of Lethane 384 and Lethane 60, and was used in the past as a treatment for pediculosis capitus (Gosselin et al, 1984; Guy, 1951; Harrison, 1947; Coulter & Creery, 1953; Lewis, 1996).
    C) USES
    1) Synthetic aliphatic thiocyanates (rhodanates) are used as contact insecticides (Gosselin et al, 1984; Plunkett, 1976). These agents are used in kerosene-based sprays and dusting powders, and are sometimes combined with rotenone, piperonyl butoxide, or pyrethrum (Gosselin et al, 1984; Sax, 1982; Lewis, 1996).
    2) LETHANE 384 -
    a) Lethane 384 is an insecticide which kills by contact activity; 50% by volume in kerosene, 1.5% dusts, 80% concentrate (Thomas, 1979)
    b) It is a knockdown agent in household aerosols; it is used in aerosol sprays with other insecticides (Thomas, 1979)
    3) THANITE -
    a) Thanite was introduced in 1945; it has mainly been used in domestic and livestock fly sprays; it contains 82% or more of the compound and about 18% related terpene esters (Hayes, 1982).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Signs and symptoms of sodium/potassium thiocyanate toxicity include nausea, vomiting, diarrhea, dermatitis, fatigue, weakness, goiter, hypotension, hallucinations, confusion, delirium, toxic psychosis, coma, seizures, cardiovascular collapse, and death. Onset of signs and symptoms may be delayed.
    B) There is some evidence that these compounds can release hydrogen cyanide after absorption; a direct depressant effect on the medullary respiratory centers may also occur.
    C) Lethane insecticide toxicity following ingestion has been reported. Some of the toxicity may be due to absorption or aspiration of the kerosene vehicle .
    D) Toxicity appears to decrease with the increase of the molecular weights of the thiocyanate homologues.
    E) Thermal decomposition may release oxides of nitrogen or sulfur.
    0.2.3) VITAL SIGNS
    A) Tachycardia, abnormal respiratory rate, and fever have been reported following lethane ingestion/aspiration.
    0.2.5) CARDIOVASCULAR
    A) Toxic effects may include bradycardia, hypotension and vascular insufficiency or collapse.
    B) Postmortem findings have included pulmonary congestion, pericardial effusion, and subendocardial hemorrhages.
    0.2.6) RESPIRATORY
    A) Following lethane ingestions, coughing, dyspnea, pneumonic sings, respiratory depression, and respiratory failure have been reported.
    B) Respiratory irritation may occur after inhalation.
    C) Pulmonary edema has been reported.
    0.2.7) NEUROLOGIC
    A) The CNS appears to be the target organ in thiocyanate poisonings. Effects may include fatigue, staggering gait, confusion, slurred speech, disorientation, toxic psychosis, seizures, coma, and death.
    B) Lethane ingestions have resulted in meningism, drowsiness, unconsciousness, and coma.
    0.2.8) GASTROINTESTINAL
    A) Nausea, vomiting, diarrhea, anorexia, esophagitis, and abdominal discomfort have been reported.
    B) Vomiting has been reported following lethane ingestion/aspiration.
    C) Postmortem findings have included corrosive and hemorrhagic gastritis.
    0.2.14) DERMATOLOGIC
    A) A maculopapular eruption and severe exfoliating dermatitis have been reported.
    0.2.15) MUSCULOSKELETAL
    A) Muscle cramping and weakness has been reported.
    0.2.16) ENDOCRINE
    A) Goiter may occur following chronic exposures.
    0.2.20) REPRODUCTIVE
    A) RATS housed in special enclosures painted with diluted or undiluted lethane 384 delivered healthy litters which grew normally.

Laboratory Monitoring

    A) Monitor CBC, serum electrolytes, BUN, creatinine, glucose, and thiocyanate level.
    B) Obtain arterial blood gas when clinically indicated.
    C) Pulse oximetry monitoring and chest radiograph should be obtained in patients with respiratory effects.
    D) It may be worthwhile to obtain serum thiocyanate and cyanide levels following exposure to thiocyanate homologues. However, the clinical usefulness of these levels is undetermined.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Begin therapy with administration of 100% oxygen. Maintain a patent airway and provide respiratory support as needed. Endotracheal intubation may be necessary. Symptomatic and supportive care is of primary importance.
    B) Induced emesis should be avoided.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    D) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    E) There have been no reports on the use of the CYANIDE ANTIDOTE KIT in the treatment of thiocyanate toxicity. The efficacy and safety of the CYANIDE ANTIDOTE KIT in this setting is unknown. As the toxicity of the aliphatic thiocyanates is presumed to be due to release of hydrogen cyanide after absorption, the treatment presented below is derived from that for cyanide poisoning. Suspected cyanide toxicity in this clinical situation should be treated with the CYANIDE ANTIDOTE KIT. Please refer to the CYANIDE management for treatment guidelines if needed.
    F) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    G) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
    H) HYPERBARIC OXYGEN AND HEMODIALYSIS: May be useful in severe cases not responsive to other therapy.
    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.
    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) An adult died after ingestion of 539 mg/kg of lethane 384 and 412.5 mg/kg of lauryl thiocyanate. A 20-month-old child survived the ingestion of between 1,750 and 3,500 mg of lethane 384.

Clinical Effects

Summary Of Exposure

    A) Signs and symptoms of sodium/potassium thiocyanate toxicity include nausea, vomiting, diarrhea, dermatitis, fatigue, weakness, goiter, hypotension, hallucinations, confusion, delirium, toxic psychosis, coma, seizures, cardiovascular collapse, and death. Onset of signs and symptoms may be delayed.
    B) There is some evidence that these compounds can release hydrogen cyanide after absorption; a direct depressant effect on the medullary respiratory centers may also occur.
    C) Lethane insecticide toxicity following ingestion has been reported. Some of the toxicity may be due to absorption or aspiration of the kerosene vehicle .
    D) Toxicity appears to decrease with the increase of the molecular weights of the thiocyanate homologues.
    E) Thermal decomposition may release oxides of nitrogen or sulfur.

Vital Signs

    3.3.1) SUMMARY
    A) Tachycardia, abnormal respiratory rate, and fever have been reported following lethane ingestion/aspiration.
    3.3.2) RESPIRATIONS
    A) Dyspnea, stertorous breathing, respiratory failure, and apnea have been reported (Coulter & Creery, 1953; Guy, 1951; Harrison, 1947).
    B) Experimental animals administered lethane 384 initially have an increased respiratory rate followed rapidly by respiratory depression (Cameron et al, 1939) von Oettingen et al, 1936).
    3.3.3) TEMPERATURE
    A) Temperature 38.2 C (100.8 F) at presentation (24 hours after lethane ingestion) was reported in a 20-mont-old boy (Guy, 1951). Aspiration bronchitis and pneumonia may have contributed to the fever.
    3.3.4) BLOOD PRESSURE
    A) Reduction in blood pressure was reported in normal and hypertensive persons following administration of thiocyanate (Healy, 1931).
    B) Cardiovascular collapse has been reported in moribund thiocyanate toxic patients (Rieves, 1984; Garvin, 1939; Wald et al, 1939).
    C) HYPOTENSION and shock were noted in a case of thanite poisoning (Hayes, 1982). Hypotension was observed in experimental animals administered lethane 384 (von Oettingen et al, 1936).
    3.3.5) PULSE
    A) Bradycardia was reported in a moribund thiocyanate toxic patient (Rieves, 1984).
    B) Tachycardia of 168 was reported in a 20-month-old boy following ingestion/aspiration of lethane (Guy, 1951).

Heent

    3.4.3) EYES
    A) Thanite is irritating to the conjunctiva (Grant & Schuman, 1993; Hayes, 1982).
    B) Nystagmus has been reported following thiocyanate exposure (Goldring & Chasis, 1932).
    C) Dilated and non-reactive pupils have been reported following lethane ingestion (Coulter & Creery, 1953).
    3.4.5) NOSE
    A) The aliphatic thiocyanates cause irritation of the mucosa of the nose and throat (Gosselin et al, 1984; Hayes, 1982; Plunkett, 1976).
    3.4.6) THROAT
    A) The aliphatic thiocyanates cause irritation of the mucosa of the nose and throat (Gosselin et al, 1984; Hayes, 1982; Plunkett, 1976).
    B) Exposed experimental animals develop excessive salivation (Cameron et al, 1939).

Cardiovascular

    3.5.1) SUMMARY
    A) Toxic effects may include bradycardia, hypotension and vascular insufficiency or collapse.
    B) Postmortem findings have included pulmonary congestion, pericardial effusion, and subendocardial hemorrhages.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) Death from cardiovascular collapse has been reported after ingestion of thanite and thiocyanate (Hayes, 1982).
    2) Bradycardia, hypotension, and vascular insufficiency or collapse have been reported (Rieves, 1984; Garvin, 1939; Wald et al, 1939). Postmortem findings of a patient who died of thiocyanate toxicity showed congestion of the lungs, pericardial effusion, and subendocardial hemorrhages (Goldring & Chasis, 1932).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPOTENSION
    a) Experimental animals administered lethane 384 developed hypotension, although the heart was noted to continue beating for a short time after respiratory arrest occurred (Cameron et al, 1939).

Respiratory

    3.6.1) SUMMARY
    A) Following lethane ingestions, coughing, dyspnea, pneumonic sings, respiratory depression, and respiratory failure have been reported.
    B) Respiratory irritation may occur after inhalation.
    C) Pulmonary edema has been reported.
    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) LETHANE - Following human ingestion/aspiration of lethane, coughing, dyspnea, heavy breathing, stertorous breathing, respiratory failure, apnea, and pneumonic signs have been reported (Coulter & Creery, 1953; Guy, 1951; Harrison, 1947).
    2) Autopsy findings in a patient following a fatal lethane ingestion showed frothy mucus in the trachea and major bronchi and some edema of the right lung (Harrison, 1947).
    B) IRRITATION SYMPTOM
    1) CASE SERIES - Volunteers exposed to an atmosphere containing 60 mg/m(3) of thanite in kerosene developed irritation of the nose and throat that was usually reversible immediately on termination of exposure (Hayes, 1982).
    C) ACUTE LUNG INJURY
    1) Pulmonary edema has occurred in oral poisoning with lethane 384 and thanite (Hayes, 1982; Harrison, 1947).
    2) If oxides of nitrogen or sulfur are released from thermal decomposition of aliphatic thiocyanates (Lewis, 1996), pulmonary edema might also develop in exposed patients (Kizer, 1984).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) APNEA
    a) Animals died from respiratory failure after being given fatal doses of Lethane 384, Lethane 384 Special, or He-60 (Main & Haag, 1942).
    2) IRRITATION
    a) Experimental animals exposed to lethane 384 vapor developed respiratory tract irritation, in some cases severe enough to be fatal (von Oettingen et al, 1936).

Neurologic

    3.7.1) SUMMARY
    A) The CNS appears to be the target organ in thiocyanate poisonings. Effects may include fatigue, staggering gait, confusion, slurred speech, disorientation, toxic psychosis, seizures, coma, and death.
    B) Lethane ingestions have resulted in meningism, drowsiness, unconsciousness, and coma.
    3.7.2) CLINICAL EFFECTS
    A) COMA
    1) The CNS appears to be the target organ in thiocyanate toxicity. Signs and symptoms include fatigue and weakness, staggering gait, confusion, rambling conversations, slurred speech associated with word aphasia, restlessness, disorientation, toxic psychosis, cerebral agitation, delusion, delirium, hallucinations, stupor, seizures, coma, and death (Rieves, 1984; Barnett et al, 1951) del Solar et al, 1949; (Garvin, 1939; Wald et al, 1939) Baker, 1936; (Goldring & Chasis, 1932).
    2) Patients ingesting lethane 384 or thanite have developed coma or CNS depression (Hayes, 1982) Harrison, 1946; (Guy, 1951; Coulter & Creery, 1953).
    B) SEIZURE
    1) Meningism, drowsiness, irritability, generalized seizures or muscular twitching, and unconsciousness have been reported following human lethane ingestion/aspiration (Guy, 1951; Coulter & Creery, 1953; Harrison, 1947).
    C) HEMIPLEGIA
    1) Episodic hemiplegia with disabling weakness, headache, and muscular tremors occurred as a result of relative hypotension in hypertensive patients being treated with thiocyanate (Wald et al, 1939).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SEIZURES
    a) Exposed experimental animals develop seizures (Cameron et al, 1939) von Oettingen et al, 1936).
    2) PARALYSIS
    a) RABBITS - Paralysis, opisthotonus, and spasticity have been described in rabbits given lethane 384 by various routes (Cameron et al, 1939; Main & Haag, 1942).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea, vomiting, diarrhea, anorexia, esophagitis, and abdominal discomfort have been reported.
    B) Vomiting has been reported following lethane ingestion/aspiration.
    C) Postmortem findings have included corrosive and hemorrhagic gastritis.
    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) Nausea, vomiting, diarrhea, anorexia, and abdominal cramps have been reported following ingestion (Plunkett, 1976; Harrison, 1947; Rieves, 1984; Garvin, 1939; Wald et al, 1939; Goldring & Chasis, 1932).
    2) Postmortem finding of petechiae along the stomach wall and duodenum was reported in a patient who died after ingesting lethane (Harrison, 1947).
    3) Vomiting was reported following lethane ingestion/aspiration (Guy, 1951; Harrison, 1947).
    B) ESOPHAGITIS
    1) Esophageal erosions or petechial hemorrhages have been noted at autopsy following a fatal thanite ingestion (Hayes, 1982).
    C) ASCITES
    1) Ascites has been reported at autopsy in one case of human thanite ingestion (Hayes, 1982).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) IRRITATION
    a) Evidence of gastrointestinal tract mucosa irritation has been found in experimental animals given oral doses of lethane 384 (Cameron et al, 1939; von Oettingen et al, 1936).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ACIDOSIS
    1) Anion gap metabolic acidosis has not been reported following human exposures to thiocyanate or lethane. The clinical presentation (coma, seizures, circulatory compromise) of aliphatic thiocyanate poisoning may result in an elevated anion gap metabolic acidosis.
    2) In vitro experiments show that thiocyanate is oxidized to sulfate and cyanide catalyzed in the erythrocyte by oxyhemoglobin (Chung & Wood, 1971). However, animal data suggests that thiocyanate has unpredictable lethal effects and its conversion to cyanide in vivo cannot account for its toxicity (Smith, 1973).

Dermatologic

    3.14.1) SUMMARY
    A) A maculopapular eruption and severe exfoliating dermatitis have been reported.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) A maculopapular itching, scaling eruption may appear, usually on the flexor surfaces of the wrists and forearms or the lower third of the leg (Wald et al, 1939; Ayman, 1929; Weis & Ruedeman, 1929). It has also been reported to appear on the face, around the corner of the eyes and lips or over the scapular region. It has spontaneously resolved on withdrawal of the thiocyanate drug.
    2) Severe exfoliating forms of dermatitis with fever, facial edema, and marked general symptoms of intoxication has also been reported (Wald et al, 1939; Ayman, 1929; Weis & Ruedeman, 1929).
    3) Severe dermal irritation has been noted in exposed experimental animals and in some human exposures (Cameron et al, 1939).
    4) Patch tests with thanite in human volunteers did not show any sensitization to the material (Hayes, 1982).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) RASH
    a) Dermal application of lethane 384 in concentrations similar to those used as insecticides did not produce undue irritation in experimental animals (Cameron et al, 1939).

Musculoskeletal

    3.15.1) SUMMARY
    A) Muscle cramping and weakness has been reported.
    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) Aching and cramping in the muscles of the calf associated with transitory periods of fatigue has been reported following thiocyanate exposures. Sensations of weakness and fatigue were reported during the first few weeks of thiocyanate therapy. These symptoms are usually relieved on discontinuation of thiocyanate therapy (Wald et al, 1939) Baker, 1936; (Healy, 1931).
    B) MUSCLE WEAKNESS
    1) Flaccid limbs has been reported in a 20-month-old male who swallowed a "small amount" of lethane 384 special (Coulter & Creery, 1953).
    C) SPASMODIC MOVEMENT
    1) Occasional "twitch" has been reported in a 20-month-old male who swallowed approximately 3.5 to 7 cc of lethane hair oil (Guy, 1951).

Endocrine

    3.16.1) SUMMARY
    A) Goiter may occur following chronic exposures.
    3.16.2) CLINICAL EFFECTS
    A) GOITER
    1) Goiter occasionally appears, usually as a diffuse, benign enlargement of the gland, with normal or slightly lowered metabolic rate (Wald et al, 1939).
    2) Thyroid enlargement has appeared after long continued administration of thiocyanate and with blood values constantly in lower brackets (Wald et al, 1939).

Reproductive

    3.20.1) SUMMARY
    A) RATS housed in special enclosures painted with diluted or undiluted lethane 384 delivered healthy litters which grew normally.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) OTHER CYANOGEN-ASSOCIATED TERATOGENESIS - Other compounds that release cyanide after absorption such as laetrile, cassava powder, acetonitrile, acrylonitrile, and propionitrile have caused teratogenic effects in the offspring of exposed experimental animals (Singh, 1981; Willhite, 1982) 1983; (Willhite et al, 1981).
    B) LACK OF EFFECT
    1) RATS housed in special enclosures painted with diluted or undiluted lethane 384 delivered healthy litters which grew normally (Cameron et al, 1939).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) At the time of this review, no information was available on whether the aliphatic thiocyanates are excreted in breast milk, or what their potential toxicity might be for the nursing infant.
    3.20.5) FERTILITY
    A) TESTIS DISORDER
    1) MALE REPRODUCTIVE EFFECTS - Some rats chronically administered aliphatic thiocyanates developed regressive testicular lesions with nearly complete absence of spermatic epithelium in the tubules, collapse of the lumina, and calcium concretions in some lumina (von Oettingen et al, 1936).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS115-31-1 (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
    B) IARC Carcinogenicity Ratings for CAS112-56-1 (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
    C) IARC Carcinogenicity Ratings for CAS301-11-1 (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
    D) IARC Carcinogenicity Ratings for CAS63917-01-1 (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
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of the aliphatic thiocyanates.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor CBC, serum electrolytes, BUN, creatinine, glucose, and thiocyanate level.
    B) Obtain arterial blood gas when clinically indicated.
    C) Pulse oximetry monitoring and chest radiograph should be obtained in patients with respiratory effects.
    D) It may be worthwhile to obtain serum thiocyanate and cyanide levels following exposure to thiocyanate homologues. However, the clinical usefulness of these levels is undetermined.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) CBC, serum electrolytes,BUN, creatinine, glucose, and thiocyanate level should be obtained.
    2) In a symptomatic patient who has been receiving prolonged nitroprusside IV infusion, serum thiocyanate, lactate and cyanide level should be obtained.
    a) The target serum thiocyanate level was 8 to 12 mg/dL when thiocyanate was used to treat hypertension (Barker, 1936).
    b) Serious manifestations of thiocyanate were not noted until levels were 35 to 50 mg/dL (Barker, 1936)
    c) Patients with renal dysfunction are at particular risk for thiocyanate toxicity.
    d) Serum cyanide level may be useful in confirming the diagnosis of cyanide toxicity from prolonged nitroprusside administration, however, it contributes little to the acute clinical management of the patient.
    3) It may be worthwhile to obtain serum thiocyanate and cyanide levels following exposure to thiocyanate homologues. However, the clinical usefulness of these levels is undetermined.
    B) ACID/BASE
    1) Arterial blood gas should be obtained when clinically indicated.
    2) Anion gap metabolic acidosis has not been reported following human exposures to thiocyanate or lethane. The clinical presentation (coma, seizures, circulatory compromise) of aliphatic thiocyanate poisoning may result in an elevated anion gap metabolic acidosis.
    4.1.3) URINE
    A) URINARY LEVELS
    1) Urine cyanide and thiocyanate levels can be obtained but are of undetermined value in poisoning with aliphatic thiocyanates. Such testing is seldom done clinically; it is more a research tool.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Pulse oximetry monitoring and chest radiograph should be obtained in patients with abnormal respiratory signs or symptoms.
    2) CHEST RADIOGRAPH
    a) Patients with abnormal respiratory signs or symptoms following significant inhalation exposure should have a chest radiograph.
    1) There may be a large percentage of kerosene in many of these products. Patients who may have aspirated these agents may have an initially normal chest x-ray. This examination should be repeated in 6 hours, or sooner if the patient develops signs or symptoms of aspiration or becomes febrile.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Patients with significant inhalation exposure to aliphatic thiocyanates, respiratory tract irritation, or clinical suspicion of pulmonary edema should have a chest x-ray.
    2) There is a large percentage of kerosene in many of these products. Patients who have aspirated these agents may have an initially normal chest x-ray. This examination should be repeated in six hours, or sooner if the patient develops symptoms or signs of hypoxemia or becomes febrile.

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) In a symptomatic patient who has been receiving prolonged nitroprusside infusion, serum thiocyanate, lactate and cyanide levels should be obtained. Target serum thiocyanate level has been reported to be 8-12 mg/dL when thiocyanate was used for treatment of hypertension. Serious clinical toxicity was not observed until levels reached 35-50 mg/dL (Barker, 1936).
    a) Serum cyanide level may be useful in confirming the diagnosis of cyanide toxicity from prolonged nitroprusside administration, however, it contributes little to the acute clinical management of the patient.
    2) Cyanide can be measured chemically by several methods but there is no time to perform this procedure in acute poisoning cases; therapy should be based on the clinical examination.
    3) BIOLOGICAL SPECIMENS - Cyanide can be liberated from biological specimens by acidification, followed by absorption in alkali and interaction with chromophoric reagents for quantification by absorbance spectroscopy (HSDB , 1990).
    4) Cyanide can also be measured in biological fluids by gas chromatography following conversion to cyanogen chloride by reaction with chloramine-T (HSDB , 1990).
    5) An ion-specific electrode method has sometimes been used for measuring cyanide in biological specimens (Bismuth et al, 1984).
    6) A fluorometric diffusion method based on detection of fluorescing p-benzoquinone derivatives can be used to determine cyanide in biological fluids (HSDB , 1990).
    7) An automated microdistillation assay technique has been developed that can provide whole blood and plasma cyanide level results in less than one-half hour (Groff et al, 1985) but is not yet generally available.

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) All symptomatic patients should be admitted to the hospital. Whenever the cyanide antidote kit is used, the patient should be admitted to the intensive care unit.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a history of significant exposure but who are asymptomatic should be observed closely in the hospital with an IV in place and initiate treatment based on the patient's clinical condition.
    1) In animals, DELAYED ONSET OF SYMPTOMS may occur up to 6 to 12 hours after exposure to various thiocyanate homologues (von Oettingen et al, 1936; Cameron et al, 1939). This may infer that at least 12 hours of clinical observation may be necessary in exposed patients who are initially asymptomatic.
    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.1) ADMISSION CRITERIA/INHALATION
    A) Patients with respiratory tract irritation or significant inhalation exposure to oxides of nitrogen or oxides of sulfur from thermal decomposition of aliphatic thiocyanates (Sax, 1982; Lewis, 1996) should be admitted for at least 24 hours of observation (Kizer, 1984).
    6.3.5) DISPOSITION/DERMAL EXPOSURE
    6.3.5.5) OBSERVATION CRITERIA/DERMAL
    A) Based on animal data of delayed onset of symptoms occurring 6 to 12 hours after exposure to various thiocyanate homologues (Cameron et al, 1939; von Oettingen et al, 1936), patients with significant dermal exposure, especially to concentrated solutions of aliphatic thiocyanates, may be at risk to develop delayed systemic toxicity and should be observed in a hospital setting for at least 6 to 12 hours.

Monitoring

    A) Monitor CBC, serum electrolytes, BUN, creatinine, glucose, and thiocyanate level.
    B) Obtain arterial blood gas when clinically indicated.
    C) Pulse oximetry monitoring and chest radiograph should be obtained in patients with respiratory effects.
    D) It may be worthwhile to obtain serum thiocyanate and cyanide levels following exposure to thiocyanate homologues. However, the clinical usefulness of these levels is undetermined.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) In severely symptomatic patients, skip these steps until other major emergency treatments including life support measures and administration of specific antidotes have been instituted.
    B) EMESIS/NOT RECOMMENDED
    1) Induced emesis should be avoided as esophageal erosions have been reported due to the irritant properties of these agents (Hayes, 1982). Avoid emesis due to the potential for seizures and coma.
    C) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) 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).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) In severely symptomatic patients, skip these steps until other major emergency treatments including life support measures and administration of specific antidotes have been instituted.
    2) Lethane insecticide is a mixture containing thiocyanate homologues, light petroleum, oil of citronella, and white mineral oil. The benefit of gastric decontamination has not been well established even when performed shortly after ingestion. There is a potential for associated petroleum or hydrocarbon aspiration. Please refer to the HYDROCARBON management for details regarding aspiration or hydrocarbon/petroleum products.
    B) EMESIS/NOT RECOMMENDED
    1) INDUCED EMESIS SHOULD BE AVOIDED as esophageal erosions have been reported due to the irritant properties of these agents (Hayes, 1982). Avoid emesis due to the potential for seizures and coma.
    C) ACTIVATED CHARCOAL
    1) 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.
    2) 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).
    D) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) OXYGEN
    1) Administer 100% oxygen to maintain an elevated PO2. Maintain a patent airway and provide respiratory support as needed. Endotracheal intubation may be necessary.
    B) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Establish and secure large bore vascular access.
    C) CYANIDE ANTIDOTE
    1) THIOCYANATE
    a) There have been no case reports of cyanide toxicity associated with the clinical use of sodium/potassium thiocyanate in the treatment of hypertension. The thiocyanates are no longer used in clinical medicine, however, thiocyanate toxicity may still be encountered when prolonged sodium nitroprusside infusion is administered (Rieves, 1984).
    1) If cyanide toxicity associated with prolonged or high dose sodium nitroprusside is suspected, the CYANIDE ANTIDOTE KIT should be used. PLEASE REFER TO THE SODIUM NITROPRUSSIDE management for details regarding the cyanide antidote kit in the treatment of cyanide toxicity associated with nitroprusside administration.
    b) There have been no reports on the use of the CYANIDE ANTIDOTE KIT in the treatment of thiocyanate toxicity. The safety and efficacy of the CYANIDE ANTIDOTE KIT in the treatment of thiocyanate or thiocyanate homologue toxicity is unknown.
    2) LETHANE
    a) Lethane insecticide is a mixture that contains various thiocyanate homologues, light petroleum, oil of citronella, and white mineral oil. These additives may contribute to the systemic and pulmonary toxicity of lethane when it is ingested or aspirated (Guy, 1951; Harrison, 1947).
    b) There have been no reports of cyanide toxicity associated with lethane ingestion or aspiration. The safety and efficacy of the CYANIDE ANTIDOTE KIT in the treatment of lethane homologue toxicity is unknown.
    3) ALIPHATIC THIOCYANATE/THIOCYANATE HOMOLOGUES
    a) There have been no reports on the use of CYANIDE ANTIDOTE KIT in the treatment of aliphatic thiocyanate or thiocyanate homologues toxicity. The safety and efficacy of the CYANIDE ANTIDOTE KIT is unknown.
    D) MONITORING OF PATIENT
    1) Obtain blood for arterial blood gases, venous pO2 or measured venous %O2 saturation, electrolytes, serum lactate, thiocyanate and whole blood cyanide levels. The clinical usefulness of these levels is undetermined.
    2) INTERPRETATION OF LABORATORY VALUES
    a) The following set of laboratory values suggest poisoning with an agent that inhibits oxidative phosphorylation (i.e., cyanide, hydrogen sulfide) (Hall & Rumack, 1986).
    b) Arteriolization of venous blood gases (elevated venous pO2 or measured venous %O2 saturation) may serve as an early clue in the diagnosis of cyanide poisoning (Hall et al, 1986; (Johnson & Mellors, 1988).
    c) Serum electrolytes: Anion gap metabolic acidosis [Na - (Cl + CO2)] is invariably present in serious cyanide poisoning. The normal anion gap is 12 to 16 mEq/L.
    d) Serum Lactate: Lactate concentrations may be elevated. The normal lactate range is 0.6 to 1.8 mEq/L (0.6 to 1.8 mmol/L).
    e) Arterial blood gas: Metabolic acidosis and respiratory alkalosis may be evident.
    f) Arterial pO2 usually remains normal until the stage of apnea or until the terminal stages of the poisoning if supplemental oxygen and assisted ventilation are provided.
    g) Fall in oxygen consumption accompanying cyanide poisoning can allow for increased oxygen content of peripheral and mixed venous blood. The presence of bright red venous blood or retinal veins suggests the possibility of cyanide poisoning.
    h) Arterio-Central Venous Measured %O2 Saturation Difference: Due to cellular inability to extract and use oxygen, more oxygen is present on the venous side. The MEASURED values of arterial and central venous %O2 saturation approach each other with MEASURED central venous %O2 saturation greater than 70%.
    i) Invasive hemodynamic and metabolic monitoring may reveal changes compatible with sepsis, e.g., metabolic acidosis, hypotension, fall in oxygen consumption, rise in mixed venous oxygen content, and a fall in arterial-venous oxygen gradient.
    3) RBC or whole blood cyanide levels may be useful to CONFIRM cyanide poisoning.
    E) ACIDOSIS
    1) METABOLIC ACIDOSIS: Treat severe metabolic acidosis (pH less than 7.1) with sodium bicarbonate, 1 to 2 mEq/kg is a reasonable starting dose(Kraut & Madias, 2010). Monitor serum electrolytes and arterial or venous blood gases to guide further therapy.
    2) Acidosis may be difficult to correct prior to administration of antidotes in serious cyanide poisoning cases (Hall et al, 1986).
    F) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    G) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    H) 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).
    I) BURN
    1) A careful abdominal examination should be done in cases of aliphatic thiocyanate ingestion. Abdominal pain or tenderness, fever, hematemesis, or hematochezia should prompt an evaluation for gastrointestinal irritation, bleeding, ulceration, or perforation. In patients with esophageal symptoms, endoscopic evaluation should be considered.
    J) PULMONARY ASPIRATION
    1) In cases of possible aspiration of aliphatic thiocyanate insecticides containing large percentages of kerosene, obtain a baseline chest x-ray. If the initial chest x-ray is normal, repeat the examination 6 hours later, or sooner if symptoms or signs of respiratory distress or fever are noted.

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) Many chemicals cause irritation of the eyes, skin, and respiratory tract. In severe cases respiratory tract irritation can progress to ARDS/acute lung injury, which may be delayed in onset for up to 24 to 72 hours in some cases.
    2) Irritation or burns of the esophagus or gastrointestinal tract are also possible if caustic or irritant chemicals are ingested.
    B) GENERAL TREATMENT
    1) Move victims from the contaminated atmosphere and administer 100% humidified supplemental oxygen with assisted ventilation as required. Endotracheal intubation may be necessary.
    2) PERSONNEL PROTECTION: In a situation where cyanide gas is suspected to be involved, rescuers should wear full protective clothing and self-contained positive pressure breathing apparatus to avoid being exposed themselves.
    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).

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) SKIN ABSORPTION
    1) Significant toxicity followed dermal exposure in experimental animals, and symptom onset was delayed for 6 to 12 hours in some cases (Cameron et al, 1939).
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) HEMODIALYSIS
    1) THIOCYANATE
    a) Renal excretion of thiocyanate is the primary means of eliminating thiocyanate and it is slow and unpredictable with the average renal clearance reported to be 2.2 cc per minute in humans with normal renal function (Danzig, 1955).
    b) Hemodialysis has been reported to be on the average 79 times more effective than normal renal clearance of thiocyanate (Danzig, 1955).
    c) Hemodialysis has been reported to be the most effective and practical procedure in the treatment of thiocyanate (psychosis) intoxication, especially in patients with renal dysfunction (Christensen & Williams, 1962; Danzig, 1955; Danzig, 1955).
    2) LETHANE
    a) There has been no report on the use of extracorporeal techniques in the management of lethane or lethane homologue toxicity.
    b) The safety and efficacy of extracorporeal techniques in the management of lethane or lethane homologue toxicity is unknown.
    3) ALIPHATIC THIOCYANATE/THIOCYANATE HOMOLOGUES
    a) There has been no report on the use of extracorporeal techniques in the management of aliphatic thiocyanate or thiocyanate homologue toxicity.
    b) The safety and efficacy of extracorporeal techniques in the management of aliphatic thiocyanate or thiocyanate homologue toxicity is unknown.

Abstracts

Case Reports

    A) INFANT
    1) LETHANE - A one-year-old child reported by Coulter & Creery (1953) ingested a "small quantity" of a 49% lethane 384 special pediculocidal hair oil. He rapidly became comatose, breathing became stertuous, cyanosis developed, generalized seizures followed, respiratory failure ensued and he became apneic. Death occurred 2.25 hours after hospital admission.
    2) LETHANE - A 20-month-old child reported by Guy (1951) swallowed between 3.5 and 7 mL of a 50% lethane 384 pediculocidal hair oil. He began coughing, became drowsy and dyspneic. Over the next 18 hours, he vomited intermittently, developed fever and had muscular "twitching". The child had drowsiness and irritability lasting about two weeks and aspiration pneumonitis with fever, but recovered. No cyanide antidotes were administered.
    B) ADULT
    1) A 35-year-old female drank a mixture containing containing an estimated 3.5 grams of Lethane 384 and 10 grams of lauryl thiocyanate and was found unconscious, breathing heavily, and had vomited. She died before arrival to the hospital (Harrison, 1947).
    a) Postmortem finding was remarkable for stomach content which contained an oily fluid with an odor of oil of citronella, petechiae along the stomach wall and duodenum, liver was acutely congested, frothy mucous was found in the trachea and major bronchi and some edema was noted in the right lung.
    2) A 56-year-old man accidentally ingested thanite (Hayes, 1982). Coma and shock developed. The patient died eight hours after ingestion. At autopsy esophageal erosions, pulmonary edema, pleural effusions, and ascites were evident. No cyanide antidotes were administered.

Range Of Toxicity

Summary

    A) An adult died after ingestion of 539 mg/kg of lethane 384 and 412.5 mg/kg of lauryl thiocyanate. A 20-month-old child survived the ingestion of between 1,750 and 3,500 mg of lethane 384.

Minimum Lethal Exposure

    A) ADULT
    1) LETHANE - A 35-year-old female was found unconscious and later died following ingestion of an estimated 0.07 milliliter/kilogram of 49% Lethane 384 (539 milligram/kilogram) and 0.206 milliliter/kilogram of 37.5 percent lauryl thiocyanate (412.5 milligram/kilogram) contained in Lethane hair oil (pediculocide) (Harrison, 1947).
    2) Isobornyl thiocyanoacetate given 4 to 5 times at a dose of 1,000 milligrams/kilogram/day can be fatal (Lehman, 1951) 1952).
    B) INFANT
    1) LETHANE - A one-year-old child ingested a "small quantity" of a lethane insecticide. He rapidly became comatose, breathing became stertouous, cyanosis developed followed by generalized seizures. Respiratory failure ensued and he became apneic. Death occurred 2.25 hours after hospital admission (Coulter & Creery, 1953).
    C) ANIMAL DATA
    1) Minimum lethal doses of Lethane 384 (50 percent solution, 500 milligram/milliliter) in various species (Cameron et al, 1939) -
    1) Rats subcutaneous - 100 mg/kg
    2) Rats intraperitoneal - 65 mg/kg
    3) Mice subcutaneous - 150 mg/kg
    4) Mice intraperitoneal - 50 mg/kg
    5) Guinea pigs subcutaneous - 200 mg/kg
    6) Guinea pigs intraperitoneal - 250 mg/kg
    7) Rabbits subcutaneous - 25 mg/kg
    8) Rabbits intraperitoneal - 25 mg/kg
    2) Lethane 384 applied to shaved skin in rats at doses of 50 to 150 milligrams resulted in some deaths (Cameron et al, 1939). All mice with dermal application of 25 milligrams to unshaved skin died (Cameron et al, 1939).

Maximum Tolerated Exposure

    A) INFANT
    1) A 20-month-old child survived the ingestion of between 3.5 and 7 milliliters of a lethane hair oil (1,750 to 3,500 milligrams of lethane 384) (Guy, 1951). Aspiration bronchitis and pneumonia from the mineral oil content of lethane was believed to contribute to the patient's clinical course. Drowsiness and irritability persisted for about 2 weeks.
    B) CASE REPORTS
    1) When 292 subjects were exposed to a 5% solution of technical thanite in a refined kerosene vehicle as a dense fog with a thanite concentration of 60 milligrams/cubic meter, they developed only mild irritation of the nose, throat, and eyes that usually subsided immediately on termination of exposure (Hayes, 1982).
    C) ANIMAL DATA
    1) In the concentrations usually employed in agriculture, no dermal toxicity of the aliphatic thiocyanates have been observed in experimental animals (Cameron et al, 1939).
    a) Aliphatic thiocyanates agents are generally considered safe when used in these dilute concentrations (Gosselin et al, 1984), but care and dermal protection must be used when handling the concentrated materials (Cameron et al, 1939).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CASE REPORTS
    a) The target serum thiocyanate level was 8 to 12 milligrams/deciliter when thiocyanate was used to treat hypertension. Serious manifestations of thiocyanate were not noted until levels were 35 to 50 milligrams/deciliter (Barker, 1936).
    b) Toxic blood or serum levels of the aliphatic thiocyanates have not been determined.

Workplace Standards

    A) ACGIH TLV Values for CAS115-31-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) ACGIH TLV Values for CAS112-56-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    C) ACGIH TLV Values for CAS301-11-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    D) ACGIH TLV Values for CAS63917-01-1 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    E) NIOSH REL and IDLH Values for CAS115-31-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    F) NIOSH REL and IDLH Values for CAS112-56-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    G) NIOSH REL and IDLH Values for CAS301-11-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    H) NIOSH REL and IDLH Values for CAS63917-01-1 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    I) Carcinogenicity Ratings for CAS115-31-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) 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
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    J) Carcinogenicity Ratings for CAS112-56-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) 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
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    K) Carcinogenicity Ratings for CAS301-11-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) 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
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    L) Carcinogenicity Ratings for CAS63917-01-1 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) 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
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    M) OSHA PEL Values for CAS115-31-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

    N) OSHA PEL Values for CAS112-56-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

    O) OSHA PEL Values for CAS301-11-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

    P) OSHA PEL Values for CAS63917-01-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LETHANE 384
    1) LD50- (ORAL)RAT:
    a) 90 mg/kg (Budavari, 1996)
    2) LD50- (SKIN)RAT:
    a) 250 mg/kg (Sax, 1982)
    B) LETHANE 60
    1) LD50- (ORAL)RAT:
    a) 500 mg/kg (Budavari, 1996)
    2) LD50- (SUBCUTANEOUS)RAT:
    a) 4300 mg/kg (Lewis, 1996)
    C) LETHANE SPECIAL
    1) LD50- (ORAL)RAT:
    a) 400 mg/kg (Lewis, 1996)
    2) LD50- (SKIN)RAT:
    a) 2500 mg/kg (Lewis, 1996)
    D) THANITE
    1) LD50- (ORAL)RAT:
    a) 1000 mg/kg (Lehman, 1951, 1952)
    b) 1000 mg/kg (Lewis, 1996)

Pharmacology Toxicology

Toxicologic Mechanism

    A) In animals the aliphatic thiocyanate insecticides are direct irritants of eyes, skin, and mucous membranes in the respiratory and gastrointestinal tracts (Gosselin et al, 1984; Hayes, 1982; Plunkett, 1976; Cameron et al, 1939; von Oettingen et al, 1936).
    B) In vitro experiments show that thiocyanate is oxidized to sulfate and cyanide catalyzed in the erythrocyte by oxyhemoglobin (Chung & Wood, 1971). However, animal data suggests that thiocyanate has unpredictable lethal effects and its conversion to cyanide in vivo cannot account for its toxicity (Smith, 1973).
    C) In animals the aliphatic thiocyanates may also cause initial respiratory stimulation followed by respiratory depression by a direct effect on the medullary respiratory centers (Cameron et al, 1939; von Oettingen et al, 1936).
    D) Thiocyanates have rapid paralytic action to insects that is attributable to the action of a thiocyano group (White-Stevens, 1971).

Physicochemical

Physical Characteristics

    A) The aliphatic thiocyanate insecticides are oily yellow to brown volatile liquids which may have the odor of kerosene with which they are often mixed (Sax, 1982; Lewis, 1996; Budavari, 1996).

Molecular Weight

    A) LETHANE 384: 203.32 (Budavari, 1996)
    B) LETHANE 60: 285.47 (Budavari, 1996)
    C) THANITE: 253.36 (Budavari, 1996)
    D) THIOCYANATE: 58 (Danzig, 1955)

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