Substances Included Synonyms

Therapeutic Toxic Class

A)

B)

Specific Substances

1) 2-Chloroethanol
2) 2-Chloroethyl alcohol
3) beta-Chloroethyl alcohol
4) delta-Chloroethanol
5) Ethanol, 2-chloro-
6) Ethylene chlorhydrin
7) Ethylene glycol, chlorohydrin
8) Glycol chlorohydrin
9) Glycomonochlorhydrin
10) Glycol monochlorohydrin
11) 2-Monochloroethanol
12) Molecular Formula: C2-H5-Cl-O
13) CAS 107-07-3
14) CHLOROETHANOL
15) CHLOROETHYL ALCOHOL

1.2.1) MOLECULAR FORMULA
1) C2-H5-Cl-O

Available Forms Sources

A)

1) At room temperature, ethylene chlorohydrin is a colorless liquid with an odor similar to that of a mixture of ethyl alcohol and ether (HSDB , 2001; Lewis & Sr, 2000; Kvistad et al, 1983). It is a very toxic solvent, with industrial poisonings reported. The vapor form has resulted in inhalational intoxications.

B)

1) Ethylene chlorohydrin is manufactured by a reaction of ethylene gas with dilute hydroochlorous acid (Bingham et al, 2001; Budavari, 1996; Lington & Bevan, 1994). A reaction of ethylene oxide with sodium chloride has also been shown to result in the formation of ethylene chlorohydrin (Oser et al, 1975). It is formed during sterilization of drugs, food products, and surgical and ophthalmic supplies with ethylene oxide.

C)

1) Ethylene chlorohydrin is used as a solvent in industry, in agriculture, and as an intermediate product in the synthesis of various chemical compounds. It is employed for the separation of butadiene from hydrocarbon mixtures, in dewaxing and removing naphthenes from mineral oil, in the refining of rosin, in the extraction of pine lignin, and as a solvent for cellulose acetate, cellulose ethers, and various resins. Formerly, its primary use was in the production of ethylene oxide, but it is no longer used in this procedure (Bingham et al, 2001; Lington & Bevan, 1994).
2) It is also used in agriculture to speed up sprouting of potatoes, to treat seeds to inhibit biological activity, and to hasten grape germination (HSDB , 2001; Lin et al, 1998).

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) SEVERE - poisoning may result in nausea, vomiting, coma, seizures, tachycardia, gastrointestinal bleeding, metabolic acidosis, hypotension, and respiratory failure. Human fatal poisonings have occurred by the oral, inhalational, and dermal exposure routes. Ethylene chlorohydrin has a moderate to high order of acute toxicity. Reported deaths have been due to metabolic acidosis and respiratory failure.
B) MILD/MODERATE - exposure may cause nausea, vomiting, tachycardia, tachypnea, weakness, lethargy, transient confusion, sore throat or mouth pain, dizziness, transient hypertension, hypokalemia and transient renal insufficiency.
C) DERMAL - Absorption through intact skin is good and dermal exposure may cause systemic toxicity. It is an eye irritant, but not a skin sensitizer. Ethylene chlorohydrin penetrates ordinary rubber gloves.
D) ONSET - Toxic effects generally develop within 2 hours after exposure.
E) When heated to decomposition, ethylene chlorohydrin releases highly toxic chloride and phosgene fumes.

0.2.3)

A) Tachypnea, hypotension, and irregular pulse may occur.

0.2.4)

A) This substance is highly irritating to the eyes and mucous membranes of the nose and throat. Visual disturbances and hemorrhages of the conjunctiva have been reported in exposed workers.

0.2.5)

A) Circulatory shock and sinus tachycardia may occur. Necrobiotic and dystrophic changes and dilation of the right side of the heart have been reported with severe poisoning.

0.2.6)

A) Respiratory tract irritation, cough, and respiratory failure have been reported. Noncardiogenic pulmonary edema, capillary engorgement, and interstitial hemorrhages of the lungs may occur.

0.2.7)

A) Incoordination, vertigo, confusion, paresthesias, spastic contracture of the hands, seizures, cerebral edema, giddiness, headache, CNS depression, weak or absent reflexes, paralysis, and mental disturbances may occur.

0.2.8)

A) Nausea and vomiting may occur.

0.2.9)

A) Liver glutathione depletion, inactivation of drug-metabolizing enzymes, hemorrhage, liver damage, and hepatic necrosis may occur.
B) In rats, oral ethanol administered concomitantly lessened the early effects on liver glutathione.

0.2.10)

A) Hematuria, slight albuminuria, polyuria, cloudy swelling of the tubules, intense engorgement, dystrophic and necrobiotic changes, degeneration of the kidneys, disorders in excretion of electrolytes and nitrogen, and hemorrhages of the kidney may occur.

0.2.11)

A) Metabolic acidosis may occur.

0.2.14)

A) Human fatalities have occurred following dermal exposure.
B) Erythema, nuclear pyknosis, blisters, and petechial skin hemorrhages have been reported in experimental animal studies.

0.2.16)

A) Disturbances in pancreatic function have occurred in experimental animals.

0.2.20)

A) Skeletal defects and developmental abnormalities of the hepatobiliary system have been noted in experimental animals.
B) Ethylene chlorohydrin was fetotoxic in mice. A significant reduction in maternal weight gain and a decrease in fetal body weight and liver weight was noted in experimental animals.

0.2.21)

A) No evidence of carcinogenicity has been found.

Laboratory Monitoring

A)

B)

C)

D)

Treatment Overview

0.4.2)

A) Do NOT induce emesis.
B) 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.

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) 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.

E) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
F) 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.
G) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.

0.4.3)

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)

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)

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)

B)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

E)

Vital Signs

3.3.1)

A) Tachypnea, hypotension, and irregular pulse may occur.

3.3.2)

A) Rapid respirations were reported in a fatal poisoning (Saitanov & Kononova, 1976).

3.3.4)

A) Decreased blood pressure has been reported in fatal human poisonings and in workers who recovered after exposure to ethylene chlorohydrin (Bush et al, 1949) Saitanov & Kononova, 1976; (Lington & Bevan, 1994).

3.3.5)

A) A weak irregular pulse has been reported following toxic human exposures (Lington & Bevan, 1994).

Heent

3.4.1)

A) This substance is highly irritating to the eyes and mucous membranes of the nose and throat. Visual disturbances and hemorrhages of the conjunctiva have been reported in exposed workers.

3.4.3)

A) Ethylene chlorohydrin produced moderate to severe irritation in the rabbit in the Standard Draize Test (RTECS , 2001). Application of undiluted ethylene chlorohydrin to rabbit eyes resulted in transient clouding of the cornea, but improvement was seen 24 hours later. Iritis and increasing conjunctival hyperemia and edema subsided within one week (Grant & Schuman, 1993).

1) McDonald et al (1977) reported the maximum nondamaging concentration of ethylene chlorohydrin to be 2 percent when applied to normal and irritated rabbit eyes in a 6 hour continuous application.

B) IRRITATION - Eye irritation has been reported in humans following exposure to airborne concentrations of 300 and 500 ppm (HSDB , 2001; Lington & Bevan, 1994).

1) Splash injuries have resulted in human corneal burns, which were reported to resolve within 48 hours (Grant & Schuman, 1993).

C) Visual disturbances have been reported in humans following acute exposure (Bingham et al, 2001; Lington & Bevan, 1994). No permanent ocular disturbances have been reported in survivors (Grant & Schuman, 1993).

3.4.5)

A) IRRITATION - Nasal irritation has been reported in workers exposed to airborne concentrations estimated to be between 300 and 500 ppm (HSDB , 2001; ACGIH, 1991).

3.4.6)

A) IRRITATION - This substance is highly irritating to the mucous membranes of the nose and throat. Sore throat and oral discomfort have been reported (Deng et al, 2001; HSDB , 2001).

Cardiovascular

3.5.1)

A) Circulatory shock and sinus tachycardia may occur. Necrobiotic and dystrophic changes and dilation of the right side of the heart have been reported with severe poisoning.

3.5.2)

A) HYPOTENSIVE EPISODE

1) Irregular weak pulse and cardiovascular shock have been reported (Deng et al, 2001; Budavari, 1996; Lington & Bevan, 1994).
2) CASE REPORT - Following ingestion of an unknown amount of ethylene chlorohydrin, a 21-month-old girl developed hypovolemic shock, noncardiogenic pulmonary edema, and severe vomiting. Full recovery followed symptomatic therapy and treatment with ethanol and methionine (Kvistad et al, 1983).

B) HYPOTENSIVE EPISODE

1) Hypotension has been reported in experimental animals and humans (Lington & Bevan, 1994). Fatal oral overdoses that present with hypotension, acidosis, and respiratory insufficiency have been reported (Deng et al, 2001).

C) TACHYARRHYTHMIA

1) CASE SERIES - 3 of 13 patients had tachycardia and chest tightness following acute oral or dermal exposure to ethylene chlorohydrin (Lin et al, 1998).

D) CARDIOVASCULAR FINDING

1) PATHOLOGY - Necrobiotic and dystrophic changes of the heart were reported in a 24-year-old with fatal poisoning (Clayton & Clayton, 1982).

3.5.3)

A) ANIMAL STUDIES

1) MYOCARDITIS

a) RATS - Subacute myocarditis was seen at necropsy in male and female rats that died shortly after changing from dietary to intragastric ethylene chlorohydrin (67.5 mg/kg/day) in a short-term toxicity study (Oser et al, 1975).

Respiratory

3.6.1)

A) Respiratory tract irritation, cough, and respiratory failure have been reported. Noncardiogenic pulmonary edema, capillary engorgement, and interstitial hemorrhages of the lungs may occur.

3.6.2)

A) APNEA

1) Respiratory failure and noncardiogenic pulmonary edema have been reported (Bingham et al, 2001; Lington & Bevan, 1994). Respiratory insufficiency has been reported, preceding death following ingestions (Deng et al, 2001).
2) CASE SERIES - Five of 13 patients died within 24 hours following acute oral exposure to ethylene chlorohydrin; respiratory failure was the cause of death (Lin et al, 1998).
3) CASE SERIES - Seven of 17 patients died within 24 hours following acute poisoning (14 oral, 2 dermal and 1 inhalation route of exposure) with ethylene chlorohydrin. Death was due to metabolic acidosis and respiratory failure (Deng et al, 2001).

B) ACUTE LUNG INJURY

1) Noncardiogenic pulmonary edema following ingestion of ethylene chlorohydrin has been reported (Kvistad et al, 1983). Fatalities with pulmonary edema have been reported following industrial exposure by inhalation or the dermal route (HSDB , 2001).

3.6.3)

A) ANIMAL STUDIES

1) PULMONARY EDEMA

a) RATS - A high incidence of congestive pulmonary changes was seen in both male and female rats in a short-term oral toxicity study (Oser et al, 1975).

Neurologic

3.7.1)

A) Incoordination, vertigo, confusion, paresthesias, spastic contracture of the hands, seizures, cerebral edema, giddiness, headache, CNS depression, weak or absent reflexes, paralysis, and mental disturbances may occur.

3.7.2)

A) COORDINATION PROBLEM

1) Incoordination, especially of the legs, as well as weakness, vertigo, dizziness, confusion, paresthesias and spastic contracture of the hands have been reported (Deng et al, 2001; Lington & Bevan, 1994).

B) SEIZURE

1) Seizures may occur following toxic exposure (Harbison, 1998; Kvistad et al, 1983).

C) CEREBROVASCULAR DISEASE

1) Hyperemia and edema of brain and meninges have been reported (Plunkett, 1976; Kvistad et al, 1983).

D) HEADACHE

1) Headaches are common following acute exposure (HSDB , 2001; Lington & Bevan, 1994).

E) COMA

1) Coma has been reported following acute exposure (oral, inhalation, or dermal) (Deng et al, 2001; HSDB , 2001; Budavari, 1996; Kvistad et al, 1983).
2) CASE REPORT - A 15-month-old boy spontaneously vomited within a few minutes of ingesting a few milliliters of a film cement containing ethylene chlorohydrin. Within 15 minutes he became drowsy, then lapsed into unconsciousness. Three hours later the child died (Kvistad et al, 1983).
3) CASE REPORT - A 21-month-old girl became stuporous within 30 minutes of ingesting a mixture of ethylene chlorohydrin, trichloroethane, and possibly methanol. Several hours later she was reported to be lightly comatose but survived (Kvistad et al, 1983).

F) HYPOREFLEXIA

1) Absent deep tendon reflexes have been reported following ingestion of ethylene chlorohydrin (Kvistad et al, 1983).

G) DELIRIUM

1) Delirium may occur following a significant acute exposure (HSDB , 2001; Budavari, 1996).

Gastrointestinal

3.8.1)

A) Nausea and vomiting may occur.

3.8.2)

A) NAUSEA AND VOMITING

1) Nausea and repeated vomiting are commonly seen with exposure to ethylene chlorohydrin (Deng et al, 2001; Bingham et al, 2001; HSDB , 2001; Lin et al, 1998; Lington & Bevan, 1994). Epigastric pain and bilious vomiting have also been reported (Lington & Bevan, 1994). In one fatal case, gastrointestinal bleeding was noted (Deng et al, 2001).

3.8.3)

A) ANIMAL STUDIES

1) VOMITING

a) DOGS - In a 90 day oral dose study in dogs, the maximum oral dosage of ethylene chlorohydrin that could be retained was 18 to 20 mg/kg/day. Severe vomiting prohibited higher dosages (Oser et al, 1975).

Hepatic

3.9.1)

A) Liver glutathione depletion, inactivation of drug-metabolizing enzymes, hemorrhage, liver damage, and hepatic necrosis may occur.
B) In rats, oral ethanol administered concomitantly lessened the early effects on liver glutathione.

3.9.2)

A) TOXIC HEPATITIS

1) Fatty degeneration, necrosis, engorgement of hepatic blood vessels, and interstitial hemorrhages have been observed (Clayton & Clayton, 1982). Severe liver damage was reported following an autopsy in a fatal case (HSDB , 2001).

3.9.3)

A) ANIMAL STUDIES

1) HEPATIC FUNCTION ABNORMAL

a) Ethylene chlorohydrin provokes a rapid depletion of hepatic glutathione due to detoxification of ECH by conjugation to glutathione and liberation of hydrogen chloride (Kvistad et al, 1983).
b) Histopathological effects in the liver have been reported in experimental animals (Lington & Bevan, 1994).

2) LIVER FATTY

a) In rats, fatty liver changes were seen in a short term toxicity study (Oser et al, 1975).

Genitourinary

3.10.1)

A) Hematuria, slight albuminuria, polyuria, cloudy swelling of the tubules, intense engorgement, dystrophic and necrobiotic changes, degeneration of the kidneys, disorders in excretion of electrolytes and nitrogen, and hemorrhages of the kidney may occur.

3.10.2)

A) BLOOD IN URINE

1) Hematuria, albuminuria, and polyuria have been reported (Lington & Bevan, 1994).

B) NEPHRITIS

1) Kidney tubules had cloudy swelling, intense engorgement, and the presence of parenchymal cells in one case, while in another reported case, there were dystrophic and necrobiotic changes (Clayton & Clayton, 1982).

Acid-Base

3.11.1)

A) Metabolic acidosis may occur.

3.11.2)

A) ACIDOSIS

1) Metabolic acidosis, often severe, may occur following ethylene chlorohydrin exposure (Deng et al, 2001; Kvistad et al, 1983).
2) CASE SERIES - Seven of 17 patients died within 24 hours following acute poisoning (14 oral, 2 dermal and 1 inhalation route of exposure) with ethylene chlorohydrin. Death was due to metabolic acidosis and respiratory failure (Deng et al, 2001).

Dermatologic

3.14.1)

A) Human fatalities have occurred following dermal exposure.
B) Erythema, nuclear pyknosis, blisters, and petechial skin hemorrhages have been reported in experimental animal studies.

3.14.2)

A) POISONING

1) Human fatalities have been reported following dermal absorption of ethylene chlorohydrin. Rubber gloves do not offer protection against this compound as laboratory analysis has shown that toxic amounts of ethylene chlorohydrin or its aqueous solutions rapidly pass through rubber. Significant skin irritation may not be present (Lington & Bevan, 1994).

B) EXCESSIVE SWEATING

1) Profuse perspiration has been reported in humans following acute exposure to ethylene chlorohydrin (Lington & Bevan, 1994).

3.14.3)

A) ANIMAL STUDIES

1) IRRITATION

a) Ethylene chlorohydrin induced mild irritation in the rabbit in the Standard Draize Test (RTECS , 2001).
b) Application of this compound in concentrations of 1 to 100 percent produced concentration-related irritation of mucous membranes in experimental animal studies. The same concentrations applied to normal skin produced little effect. Absorption may occur without irritation.

Endocrine

3.16.1)

A) Disturbances in pancreatic function have occurred in experimental animals.

3.16.3)

A) ANIMAL STUDIES

1) PANCREATIC DISORDER

a) Disturbances in pancreatic function were noted in experimental animals following exposure to ethylene chlorohydrin (Strusevich et al, 1976).

2) ADRENAL HEMORRHAGE

a) Oser et al (1975) reported hemorrhagic adrenal and pituitary glands in rats that died during a short-term toxicity study.

Reproductive

3.20.1)

A) Skeletal defects and developmental abnormalities of the hepatobiliary system have been noted in experimental animals.
B) Ethylene chlorohydrin was fetotoxic in mice. A significant reduction in maternal weight gain and a decrease in fetal body weight and liver weight was noted in experimental animals.

3.20.2)

A) CONGENITAL ANOMALY

1) In the mouse, specific developmental abnormalities of the hepatobiliary system were observed (RTECS , 2001).

B) FETOTOXICITY

1) Fetotoxicity and teratogenicity have been reported. Chromosome abnormalities have been reported in rats exposed to an airborne concentration of 0.22 ppm (ACGIH, 1991).

3.20.3)

A) EMBRYOTOXICITY

1) Dose-related increases in defective chick embryos have been noted. Other studies failed to find malformations when ethylene chlorohydrin was administered orally or by inhalation (ACGIH, 1991).

B) WEIGHT DECREASE

1) Mice were given ethylene chlorohydrin from day 6 to 16 of gestation at a dose of 100 mg/kg. A significant reduction in maternal weight gain and a decrease in fetal body weight and liver weight were noted (Courtney et al, 1982).

C) FETOTOXICITY

1) Ethylene chlorohydrin was fetotoxic in the mouse (RTECS , 2001).

3.20.4)

A) LACK OF INFORMATION

1) At the time of this review, no human or experimental animal data were available to assess the potential effects of exposure to this agent during lactation.

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS107-07-3 (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

3.21.2)

A) No evidence of carcinogenicity has been found.

3.21.3)

A) OCCUPATIONAL EXPOSURE

1) Olsen et al (1997) reported no increased risk of pancreatic cancer and lymphopoietic and hematopoietic carcinomas in a workplace cohort of 1361 men at an ethylene and propylene chlorohydrin production plant during the years 1940 to 1992. All workers had at least 30 days of workplace experience.

B) LACK OF EFFECT

1) No evidence of carcinogenicity was found in NTP Carcinogenesis Studies in the mouse and rat (Lewis & Sr, 2000).

Genotoxicity

A)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) No toxic blood or urine levels have been established.
B) Monitor hepatic and renal function tests.
C) Monitor vital signs.
D) Monitor chest x-ray and arterial blood gases or pulse oximetry in patients with respiratory distress.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) No toxic serum, blood, or urine levels have been established.
2) Monitor hepatic and renal function tests.
3) Monitor fluid and electrolyte balance in patients with extensive vomiting and/or diarrhea.

4.1.3)

A) URINALYSIS

1) Monitor for urinary protein/albumin and hematuria in symptomatic patients.

4.1.4)

A) OTHER

1) PULMONARY FUNCTION TESTS

a) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.

2) OXYGENATION

a) Monitor arterial blood gases or pulse oximetry in patients with respiratory distress.

Radiographic Studies

A)

1) If respiratory tract irritation is present, monitor chest x-ray.

Methods

A)

1) Gas chromatography with flame ionization detection has been used to detect ethylene chlorohydrin in items after ethylene oxide sterilization and in spices and condiments (Muzeni, 1985; Aitkenhead & Vidnes, 1988)
2) A rapid gas chromatographic method using water to extract ethylene chlorohydrin has been described (Merckx & Kinget, 1986).

B)

1) A study was performed sampling ethylene chlorohydrin in workroom air using activated charcoal. The authors concluded that the use of activated charcoal as an adsorbent for ethylene chlorohydrin from air had several disadvantages including poor recoveries and decomposition of the sampled compounds (Andersson et al, 1981).

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) All symptomatic patients should be admitted to the hospital. Symptoms may occur within 3 hours of exposure. Symptomatic patients should be monitored for at least 48 hours for level of consciousness, respirations, seizures, and blood pressure.

6.3.3)

6.3.3.5) OBSERVATION CRITERIA/INHALATION

A) All symptomatic patients should be admitted to the hospital. Symptoms may occur within 3 hours of exposures. Symptomatic patients should be monitored for at least 48 hours, for level of consciousness, respirations, seizures, and blood pressure.

6.3.5)

6.3.5.5) OBSERVATION CRITERIA/DERMAL

A) All symptomatic patients should be admitted to the hospital. Symptoms may occur within 3 hours of exposures. Symptomatic patients should be monitored for at least 48 hours, for level of consciousness, respirations, seizures, and blood pressure.

Monitoring

A)

B)

C)

D)

Oral Exposure

6.5.1)

A) EMESIS/NOT RECOMMENDED -

1) EMESIS: Ipecac-induced emesis is not recommended because of the potential for CNS depression.

B) 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).

C) INHALATION -

1) 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.
2) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
3) 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.

D) DERMAL -

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).

E) EYE -

1) 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).

6.5.2)

A) EMESIS/NOT RECOMMENDED

1) Do NOT induce emesis.

B) 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).

C) 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)

A) 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).

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) 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).

D) AIRWAY MANAGEMENT

1) Monitor respirations. Intubate and ventilate as clinically indicated.

E) MONITORING OF PATIENT

1) Monitor liver and kidney functions for abnormalities. Monitor fluid and electrolytes when extensive vomiting and/or diarrhea occurs. Replace fluids as necessary.

F) EXPERIMENTAL THERAPY

1) ETHANOL THERAPY -

a) Toxicity in experimental animals was decreased by simultaneous ethanol administration (Johnson, 1967; Johnson, 1975), possibly due to ethanol competitively inhibiting the ethylene chlorohydrin from being converted to the more toxic chloroacetaldehyde via dehydrogenation.
b) An ethanol infusion was administered over a 4 day period in conjunction with infusions of methionine and other amino acids for an accidental overdose of ethylene chlorohydrin by a 21-month-old girl who fully recovered (Kvistad et al, 1983). Further data are needed to substantiate this regimen before it could be generally recommended.

1) ETHANOL THERAPY - Ethanol (ETOH) partially inhibits the formation of toxic metabolites. LOADING DOSE - Administer 10 mL/kg of 10 percent ETOH in D5W over 30 minutes. MAINTENANCE DOSE - Administer 1 to 2 mL/kg/hr of 10 percent ETOH in D5W by IV infusion. Aim at achieving and maintaining 100 to 130 mg/dL blood ethanol levels. PRECAUTION - Monitor blood glucose and ETOH levels.

2) N-ACETYLCYSTEINE (NAC)

a) N-Acetylcysteine (NAC) - Although not an established therapy for ethylene chlorohydrin poisonings, it may be helpful to promote resynthesis of glutathione in liver cells and increase conjugation and detoxification.

1) ORAL NAC DOSING - The most common dosing regimen in the US is a loading dose of 140 milligrams/kilogram diluted to a 5 percent solution followed by 70 milligrams/kilogram administered every 4 hours. The duration of therapy has not been established for ethylene chlorohydrin. For acetaminophen poisoning, treatment is continued for 17 70 milligrams/kilogram maintenance doses.
2) INTRAVENOUS NAC DOSING - The European protocol for intravenous administration of N-Acetylcysteine is: 150 milligrams/kilogram NAC in 200 milliliters of D5W administered over 15 minutes followed by 50 milligrams/kilogram in 500 milliliters D5W infused over the next 4 hours. Finally, 100 milligrams/kilogram NAC in 1000 milliliters D5W is infused over the next 16 hour period.

G) IRRITATION SYMPTOM

1) Observe patients with ingestion carefully for the possible development of esophageal or gastrointestinal tract irritation or burns. If signs or symptoms of esophageal irritation or burns are present, consider endoscopy to determine the extent of injury.

Inhalation Exposure

6.7.1)

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)

A) SUPPORT

1) Inhalational absorption of ethylene chlorohydrin has occurred. Symptomatology appears to be similar to that seen following ingestion. Treatment is similar.

B) 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).

C) 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).

D) 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).

E) MONITORING OF PATIENT

1) Monitor liver and kidney functions for abnormalities. Monitor fluid and electrolytes when extensive vomiting and/or diarrhea occurs. Replace fluids as necessary.
2) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.

F) EXPERIMENTAL THERAPY

1) ETHANOL -

a) Toxicity in experimental animals was decreased by simultaneous ethanol administration (Johnson, 1967; Johnson, 1975), possibly due to ethanol competitively inhibiting the ethylene chlorohydrin from being converted to the more toxic chloroacetaldehyde via dehydrogenation.
b) In a single case of ingestion of ethylene chlorohydrin, an ethanol infusion and methionine and amino acid infusions were administered for 3 days to a 21-month-old girl who fully recovered (Kvistad et al, 1983). Further data are needed to substantiate this regiment before it could be generally recommended.

1) ETHANOL THERAPY - Ethanol (ETOH) partially inhibits the formation of toxic metabolites. LOADING DOSE - Administer 10 mL/kg of 10 percent ETOH in D5W over 30 minutes. MAINTENANCE DOSE - Administer 1 to 2 mL/kg/hr of 10 percent ETOH in D5W by IV infusion. Aim at achieving and maintaining 100 to 130 mg/dL blood ethanol levels. PRECAUTION - Monitor blood glucose and ETOH levels.

2) N-ACETYLCYSTEINE (NAC) -

a) N-Acetylcysteine (NAC) - Although not an established therapy for ethylene chlorohydrin poisonings, it may be helpful to promote resynthesis of glutathione in liver cells and increase conjugation and detoxification.

1) INTRAVENOUS NAC DOSING - The European protocol for intravenous administration of N-Acetylcysteine is: 150 milligrams/kilogram NAC in 200 milliliters of D5W administered over 15 minutes followed by 50 milligrams/kilogram in 500 milliliters D5W infused over the next 4 hours. Finally, 100 milligrams/kilogram NAC in 1000 milliliters D5W is infused over the next 16 hour period.
2) ORAL NAC DOSING - The most common dosing regimen in the US is a loading dose of 140 milligrams/kilogram diluted to a 5 percent solution followed by 70 milligrams/kilogram administered every 4 hours. The duration of therapy has not been established for ethylene chlorohydrin. For acetaminophen poisoning, treatment is continued for 17 70 milligram/kilogram maintenance doses.

G) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

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)

A) CORNEAL BURN

1) Accidental liquid splash contacts to the eyes may result in corneal burns, which have been reported to recover within 48 hours (Grant & Schuman, 1993).
2) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

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)

A) SKIN ABSORPTION

1) Dermal absorption of ethylene chlorohydrin has occurred, even through protective rubber gloves. A fatality has been reported due to apparent cutaneous absorption of this chemical (Lington & Bevan, 1994). Symptomatology appears similar to that seen following ingestion. Treatment is similar.

B) 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).

C) 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).

D) 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).

E) MONITORING OF PATIENT

1) Monitor liver and kidney function tests.

F) EXPERIMENTAL THERAPY

1) ETHANOL -

a) Toxicity in experimental animals was decreased by simultaneous ethanol administration (Johnson, 1967; Johnson, 1975), possibly due to ethanol competitively inhibiting the ethylene chlorohydrin from being converted to the more toxic chloroacetaldehyde via dehydrogenation.
b) In a single case of ingestion of ethylene chlorohydrin, an ethanol infusion and methionine and amino acid infusions were administered for 3 days to a 21-month-old girl who fully recovered (Kvistad et al, 1983). Further data are needed to substantiate this regimen before it could be generally recommended.

1) ETHANOL THERAPY - Ethanol (ETOH) partially inhibits the formation of toxic metabolites. LOADING DOSE - Administer 10 mL/kg of 10 percent ETOH in D5W over 30 minutes. MAINTENANCE DOSE - Administer 1 to 2 mL/kg/hr of 10 percent ETOH in D5W by IV infusion. Aim at achieving and maintaining 100 to 130 mg/dL blood ethanol levels. PRECAUTION - Monitor blood glucose and ETOH levels.

2) N-ACETYLCYSTEINE (NAC) -

a) N-Acetylcysteine (NAC) - Although not an established therapy for ethylene chlorohydrin poisonings, it may be helpful to promote resynthesis of glutathione in liver cells and increase conjugation and detoxification.

1) INTRAVENOUS NAC DOSING - The European protocol for intravenous administration of N-Acetylcysteine is: 150 milligrams/kilogram NAC in 200 milliliters of D5W administered over 15 minutes followed by 50 milligrams/kilogram in 500 milliliters D5W infused over the next 4 hours. Finally, 100 milligrams/kilogram NAC in 1000 milliliters D5W is infused over the next 16 hour period.
2) ORAL NAC DOSING - The most common dosing regimen in the US is a loading dose of 140 milligrams/kilogram diluted to a 5 percent solution followed by 70 milligrams/kilogram administered every 4 hours. The duration of therapy has not been established for ethylene chlorohydrin. For acetaminophen poisoning, treatment is continued for 17 70 milligram/kilogram maintenance doses.

G) IRRITATION SYMPTOM

1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

H) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

A)

1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Abstracts

Case Reports

A)

1) A 21-month-old girl accidently ingested an unknown amount of photo film cements containing ethylene chlorohydrin. Vomiting began within 30 minutes, followed by drowsiness. On admission to the hospital, a moderate metabolic acidosis was reported and light coma developed within a few hours. Hypovolemic shock (systolic BP of 35 mmHg), noncardiogenic pulmonary edema, and tachypnea ensued. Deep tendon reflexes were absent (Kvistad et al, 1983).

a) Laboratory analysis revealed leukocytosis (WBC 27 x 10(9)/L with a relative granulocytosis), pH 7.28, base deficit 15 mmol/L and hypocapnia. Shock was reversed with colloidal IV solutions, and sodium bicarbonate was given to reverse acidosis. IV infusions of methionine and amino acids were started.
b) An ethanol infusion was started, which was maintained for 3 to 4 days due to suspicion of methanol possibly contained in one of the cements. The girl was discharged 7 days after the ingestion with no reported sequelae (Kvistad et al, 1983).

B)

1) Lin et al (1998) report a retrospective case series of 13 patients, ranging in age from 2 years to 62 years of age, with acute ethylene chlorohydrin poisonings. The most common route of exposure was oral (84.6 percent), with 5 fatalities. A suicidal ingestion of 20 to 30 mL resulted in death within 3 hours in a 55-year-old male. The major cause of death in all 5 fatalities was respiratory failure. Symptoms reported in 3 survivors included nausea, vomiting, dizziness, tachycardia and chest pain. No sequelae were reported in the 8 survivors.

Range Of Toxicity

Summary

A)

B)

Minimum Lethal Exposure

A)

1) ORAL - 20 milliliters (345 milligrams/kilogram) ingested by an adult caused death three days postexposure (ACGIH, 1991).
2) In a 2-year-old child, ingestion of 1 to 2 milliliters caused death within 12 hours (HSDB , 2001; ACGIH, 1991).
3) Death occurred in 3 hours in a 15-month-old boy following ingestion of a few milliliters of a film cement containing ethylene chlorohydrin (Kvistad et al, 1983).
4) In a series of 17 patients with ethylene chlorohydrin intoxication, the average dose in fatal cases was 2467 mg/kg compared with 91 mg/kg in survivors. Ingestion of 412 milligrams/kilogram was fatal in one adult (Deng et al, 2001).

B)

1) INHALATION -

a) A 2 hour exposure to an estimated airborne concentration of 300 parts per million was fatal (ACGIH, 1991). Airborne concentrations of 300 to 500 parts per million (for an unspecified period) produced nausea, vomiting, eye, lung, and mucous membrane irritation, and severe liver damage leading to death in one worker (ACGIH, 1991).
b) RATS - Airborne concentrations of 900 to 1000 parts per million for 15 minutes/day were fatal in a few days. A single exposure to an airborne concentration of 7.5 parts per million and repeated 1 hour exposures to 2 parts per million produced fatalities.
c) UNSPECIFIED SPECIES - 2 to 8 exposures to airborne concentrations of 700 to 800 parts per million were fatal.

2) DERMAL-

a) GUINEA PIGS - As little as 0.1 milliliter (100 percent concentration) applied to the skin of guinea pigs was fatal within 24 hours (Wahlberg & Boman, 1978).
b) DERMAL - Extrapolation of experimental animal data would indicate that as little as a teaspoonful of pure ethylene chlorohydrin spilled on the skin, if not immediately washed off, could be fatal to a 70 kilogram human (Clayton & Clayton, 1994) Sittig, 1991).

C)

1) LCLo - (INHL) HUMAN, Male: 305 ppm for 2H (RTECS , 2001)

Maximum Tolerated Exposure

A)

1) The maximum tolerated human exposure to this agent has not been delineated.

B)

1) Occupational exposure to an airborne concentration of 18 parts per million caused symptoms but no fatalities (Lington & Bevan, 1994).
2) Several nonfatal exposures were reported at airborne concentrations of 300 to 500 parts per million for an unspecified time period. One fatality also occurred at this exposure level (HSDB , 2001; Lington & Bevan, 1994).

C)

1) EYE - Grant & Schuman (1993) report a maximum non-toxic eye exposure to be 0.5 percent aqueous ethylene chlorohydrin solution.

Workplace Standards

A)

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) Ethylene chlorohydrin

a) TLV:

1) TLV-TWA:
2) TLV-STEL:
3) TLV-Ceiling: 1 ppm

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): CNS impair; liver and kidney dam
d) Molecular Weight: 80.52

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 CAS107-07-3 (National Institute for Occupational Safety and Health, 2007):

1) Listed as: Ethylene chlorohydrin
2) REL:

a) TWA:
b) STEL:
c) Ceiling: 1 ppm (3 mg/m(3))
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):

3) IDLH:

a) IDLH: 7 ppm
b) Note(s): Not Listed

C) Carcinogenicity Ratings for CAS107-07-3 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Ethylene chlorohydrin

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.

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 ; Listed as: Ethylene chlorohydrin
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS107-07-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Listed as: Ethylene chlorohydrin
2) Table Z-1 for Ethylene chlorohydrin:

a) 8-hour TWA:

1) ppm: 5

a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.

2) mg/m3: 16

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: Yes
5) Notation(s): Not Listed

Toxicity Information

7.7.1)

A) References: RTECS, 2001

1) LD50- (INTRAPERITONEAL)MOUSE:

a) 97 mg/kg

2) LD50- (ORAL)MOUSE:

a) 81 mg/kg

3) LD50- (SUBCUTANEOUS)MOUSE:

a) 98 mg/kg

4) LD50- (ORAL)RAT:

a) 71 mg/kg

5) LD50- (SKIN)RAT:

a) 293 mg/kg

6) LD50- (SUBCUTANEOUS)RAT:

a) 84 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

A)

B)

1) Chloroacetaldehyde is highly cytotoxic. It is detoxified in the liver by conjugation to glutathione with subsequent liberation of hydrogen chloride, thus resulting in rapid depletion of liver glutathione (Kvistad et al, 1983).

Physicochemical

Physical Characteristics

A)

B)

Molecular Weight

A)

Other

A)

1) 0.4 ppm (ACGIH, 1991)

Animal Toxicology

References

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ETHYLENE CHLOROHYDRIN

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Dermatologic

Endocrine

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Case Reports

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

Other

General Bibliography