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CROTONALDEHYDE (E)-

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Crotonaldehyde(E) is irritating to the eyes, skin, and mucous membranes.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C4-H6-O

Overview

Laboratory Monitoring

    A) Baseline arterial blood gases and chest x-ray should be obtained for patients with significant respiratory exposure. Baseline liver and renal function tests and complete blood count with differential are suggested for patients with substantial exposure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Because of the potential for gastrointestinal tract irritation and seizures, emesis should NOT be induced.
    B) 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.
    C) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
    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) Obtain baseline liver and renal function tests and complete blood count.
    F) 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) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) 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.
    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).
    2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

Range Of Toxicity

    A) The minimum lethal exposure to crotonaldehyde is not well established. Eye and upper respiratory tract irritation occur after 10 minutes of exposure to an airborne concentration of 10 ppm and within seconds at 45 ppm.

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Crotonaldehyde is very irritating to the eyes, skin, and mucous membranes. Corneal damage may occur. Respiratory tract irritation and delayed noncardiogenic pulmonary edema are possible. Allergic contact dermatitis may be seen. Seizures have been seen in experimental animals only.
    0.2.4) HEENT
    A) Eye irritation is common. Corneal injury may occur from direct eye contact. Irritation of the nose and throat may occur.
    0.2.6) RESPIRATORY
    A) Upper respiratory tract irritation frequently occurs with crotonaldehyde inhalation. Delayed onset of noncardiogenic pulmonary edema is possible with inhalation.
    0.2.7) NEUROLOGIC
    A) Seizures have been observed as a terminal event in exposed rats.
    0.2.8) GASTROINTESTINAL
    A) GI tract irritation may be predicted to occur following ingestion based on the other irritant properties of this substance.
    0.2.9) HEPATIC
    A) Experimental animals have developed spleen and liver injury.
    0.2.14) DERMATOLOGIC
    A) Crotonaldehyde is highly irritating to exposed skin. Allergic contact dermatitis has been described.
    0.2.16) ENDOCRINE
    A) Damage to the thymus and adrenal glands has been described in exposed experimental animals.
    0.2.20) REPRODUCTIVE
    A) Chronically exposed Russian workers developed unspecified sexual disturbances, decreased androgenous function of the male endocrine glands, and menstrual disturbances.

Clinical Effects

Summary Of Exposure

    A) Crotonaldehyde is very irritating to the eyes, skin, and mucous membranes. Corneal damage may occur. Respiratory tract irritation and delayed noncardiogenic pulmonary edema are possible. Allergic contact dermatitis may be seen. Seizures have been seen in experimental animals only.

Heent

    3.4.1) SUMMARY
    A) Eye irritation is common. Corneal injury may occur from direct eye contact. Irritation of the nose and throat may occur.
    3.4.3) EYES
    A) CONJUNCTIVITIS - Lacrimation and eye irritation occur with exposure to crotonaldehyde vapor (Hathaway et al, 1991).
    B) CORNEAL DAMAGE - Corneal injury has been reported from direct contact, but healing was complete in 48 hours (Hathaway et al, 1991).
    3.4.5) NOSE
    A) IRRITATION of nasal mucous membranes occurs with inhalation exposure (Hathaway et al, 1991).
    3.4.6) THROAT
    A) IRRITATION of pharyngeal mucosa occurs with inhalation exposure (Hathaway et al, 1991).

Respiratory

    3.6.1) SUMMARY
    A) Upper respiratory tract irritation frequently occurs with crotonaldehyde inhalation. Delayed onset of noncardiogenic pulmonary edema is possible with inhalation.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) Upper respiratory tract irritation is seen in inhalation exposures (Hathaway et al, 1991). Rats exposed to high concentrations developed an excitatory phase and then severe respiratory distress, with bronchiolar injury found at autopsy (Hathaway et al, 1991).
    B) ACUTE LUNG INJURY
    1) Noncardiogenic pulmonary edema has been observed in laboratory animals (Hathaway et al, 1991).

Neurologic

    3.7.1) SUMMARY
    A) Seizures have been observed as a terminal event in exposed rats.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) Seizures have been observed in rats exposed to high concentrations by inhalation, but occurred only as a terminal event (Hathaway et al, 1991).

Gastrointestinal

    3.8.1) SUMMARY
    A) GI tract irritation may be predicted to occur following ingestion based on the other irritant properties of this substance.
    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL IRRITATION
    1) Based on this compound's other irritant properties, esophageal or GI tract irritation would be predicted to occur following ingestion.

Hepatic

    3.9.1) SUMMARY
    A) Experimental animals have developed spleen and liver injury.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) Crotonaldehyde produced moderate to severe liver injury in 10 of 23 rats with chronic ingestion (Chung et al, 1986). Injection of crotonaldehyde intraperitoneally to mice produced elevations of lactate dehydrogenase (Warholm et al, 1984).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SPLEEN DISORDER
    a) Intraperitoneal injection of crotonaldehyde to mice has produced splenic injury (Warholm et al, 1984).

Dermatologic

    3.14.1) SUMMARY
    A) Crotonaldehyde is highly irritating to exposed skin. Allergic contact dermatitis has been described.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Crotonaldehyde is an extreme skin irritant with dermal contact (Hathaway et al, 1991).
    B) CONTACT DERMATITIS
    1) One case of a textile worker with allergic contact dermatitis to dimethoxane in an aqueous phase spin finish also demonstrated sensitization to crotonaldehyde (Shmunes & Kempton, 1980).

Endocrine

    3.16.1) SUMMARY
    A) Damage to the thymus and adrenal glands has been described in exposed experimental animals.
    3.16.2) CLINICAL EFFECTS
    A) DISORDER OF ENDOCRINE SYSTEM
    1) Intraperitoneal injection to mice has caused thymic injury (Warholm et al, 1984).
    B) ADRENAL CORTICAL HYPOFUNCTION
    1) Intraperitoneal injection to mice has caused adrenal injury (Warholm et al, 1984).

Reproductive

    3.20.1) SUMMARY
    A) Chronically exposed Russian workers developed unspecified sexual disturbances, decreased androgenous function of the male endocrine glands, and menstrual disturbances.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS123-73-9 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.4) ANIMAL STUDIES
    A) HEPATIC CARCINOMA
    1) Chronic oral administration to rats produced liver neoplasms in 9 of 27 animals (Chung et al, 1986).
    B) CHROMOSOME DISORDER
    1) Crotonaldehyde is mutagenic in Drosophila (Woodruff et al, 1985) and Salmonella typhimurium (Lijinsky & Andrews, 1980).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Baseline arterial blood gases and chest x-ray should be obtained for patients with significant respiratory exposure. Baseline liver and renal function tests and complete blood count with differential are suggested for patients with substantial exposure.
    4.1.2) SERUM/BLOOD
    A) ACID/BASE
    1) Baseline arterial blood gases should be obtained in patients with significant inhalation exposure and respiratory tract irritation.
    B) BLOOD/SERUM CHEMISTRY
    1) LIVER FUNCTION TESTS - Patients with significant ingestions should have monitoring of liver function tests, particularly lactate dehydrogenase (LDH).
    C) HEMATOLOGIC
    1) WHITE BLOOD COUNT WITH DIFFERENTIAL - Patients with significant exposure could theoretically have decreased T-lymphocyte counts from thymic injury.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Baseline chest x-ray should be obtained in patients with significant inhalation exposure and respiratory tract irritation.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Baseline arterial blood gases and chest x-ray should be obtained for patients with significant respiratory exposure. Baseline liver and renal function tests and complete blood count with differential are suggested for patients with substantial exposure.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    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) Significant esophageal or gastrointestinal tract irritation or burns may occur following ingestion. The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of bleeding or perforation.
    2) 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.
    3) 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.
    4) 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.
    5) 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).
    6) 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) SUPPORT
    1) Human ingestions have not been reported. Based on experimental animal data (Warholm et al, 1984), injury to liver, spleen, adrenal glands, and thymus might occur.
    2) Baseline liver and renal function tests and complete blood count with differential are suggested.
    3) Patients with ingestions should be followed clinically for injury to the above organs.
    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) 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) 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) 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).
    B) OBSERVATION REGIMES
    1) Patients with significant inhalation exposure or respiratory irritation should be observed for delayed development of pulmonary edema.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).
    6.8.2) TREATMENT
    A) GENERAL TREATMENT
    1) Treatment is SYMPTOMATIC and SUPPORTIVE.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) ACUTE ALLERGIC REACTION
    1) ALLERGIC CONTACT DERMATITIS - may occur and may respond to treatment with antihistamines or corticosteroids. Further exposure should be prevented.
    B) 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.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) The minimum lethal exposure to crotonaldehyde is not well established. Eye and upper respiratory tract irritation occur after 10 minutes of exposure to an airborne concentration of 10 ppm and within seconds at 45 ppm.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal exposure for crotonaldehyde has not been defined.

Maximum Tolerated Exposure

    A) CONCENTRATION LEVEL
    1) Eye and upper respiratory tract irritation occurs after 10 minutes of exposure to an air concentration of 4 ppm (Hathaway et al, 1991).
    2) Conjunctival irritation appears within seconds of exposure to an airborne concentration of 45 ppm (Hathaway et al, 1991).

Workplace Standards

    A) ACGIH TLV Values for CAS123-73-9 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS123-73-9 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS123-73-9 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): C ; Listed as: Crotonaldehyde
    a) C : Possible human carcinogen.
    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): Category 3B ; Listed as: Crotonaldehyde
    a) Category 3B : Substances for which in vitro or animal studies have yielded evidence of carcinogenic effects that is not sufficient for classification of the substance in one of the other categories. Further studies are required before a final decision can be made. A MAK value can be established provided no genotoxic effects have been detected. (Footnote: In the past, when a substance was classified as Category 3 it was given a MAK value provided that it had no detectable genotoxic effects. When all such substances have been examined for whether or not they may be classified in Category 4, this sentence may be omitted.)
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS123-73-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Crotonaldehyde
    2) Table Z-1 for Crotonaldehyde:
    a) 8-hour TWA:
    1) ppm: 2
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 6
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 1996
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 160 mg/kg
    2) LD50- (ORAL)MOUSE:
    a) 240 mg/kg
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 160 mg/kg
    4) LD50- (SUBCUTANEOUS)RAT:
    a) 140 mg/kg
    5) TCLo- (INHALATION)HUMAN:
    a) 12mg/m3 for 10M

Physicochemical

Physical Characteristics

    A) Crotonaldehyde (E) is a water-white, mobile liquid with a pungent and suffocating odor (Lewis, 1996).

Molecular Weight

    A) 70.09

References

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