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CYCLOHEXANOL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Cyclohexanol is an organic alcohol used as a raw material in manufacturing, and as a solvent, in lacquers, and as an insecticide.

Specific Substances

    1) Hexahydrophenol
    2) Cyclohexyl alcohol
    3) Hexalin
    4) Hydrophenol
    5) CAS 108-93-0
    6) CICLOESANOLOL (ITALIAN)
    1.2.1) MOLECULAR FORMULA
    1) C6-H12-O

Available Forms Sources

    A) FORMS
    1) Cyclohexanol exists as a hygroscopic, viscous, colorless liquid or a sticky, colorless solid. Its odor has been described as camphor-like or menthol-like (AAR, 2000; ACGIH, 1991; Ashford, 2001) Bingham et al, 2001; (Budavari, 1996) Hathaway, 1996; (Lewis, 2000; Lewis, 2001; Verschueren, 1983).
    2) It is available in a technical grade which contains a freezing inhibitor (Lewis, 2001).
    B) SOURCES
    1) The most common industrial process used to prepare cyclohexanol is the oxidation of cyclohexane to a mixture of cyclohexanol and cyclohexanone. Other processes include the catalytic air oxidation of cyclohexane and the catalytic hydrogenation of phenol (ACGIH, 1991; Ashford, 2001) Bingham et al, 2001; (Lewis, 1997) Synder, 1992).
    2) It may be found in small concentrations (0.5-1.0%) in crude petroleum (Baselt, 1997).
    C) USES
    1) Cyclohexanol is used to produce soap and detergents, degreasers, laquers, varnishes, plastics and plasticizers, textiles, insecticides, germicides, and as the source of adipic acid in the production of nylon (AAR, 2000; ACGIH, 1991) Bingham et al, 2001; Hathaway, 1996; (Lewis, 2001) Synder, 1992
    2) When combined with thymol or triacetin, cyclohexanol has been used in the treatment of tinea pedis (HSDB , 2002).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Exposure may occur by inhalation, ingestion, or percutaneous routes. Data on toxic effects in humans are limited. Cyclohexanol is an eye, nose, throat, and skin irritant. Central nervous system depression may occur.
    B) Signs and symptoms of exposure may include seizures, ataxia, lacrimation, corneal necrosis, salivation, nausea, vomiting, and diarrhea. Kidney, liver, and vascular injury and myocardial necrosis have been reported in experimental animals.
    0.2.4) HEENT
    A) Conjunctivitis, lacrimation, and irritation of mucous membranes may occur.
    0.2.5) CARDIOVASCULAR
    A) Myocardial necrosis was observed in animals.
    0.2.7) NEUROLOGIC
    A) Headache, tremor, and CNS depression may occur.
    0.2.8) GASTROINTESTINAL
    A) Nausea and vomiting have been reported.
    0.2.9) HEPATIC
    A) Liver damage was observed in animals.
    0.2.10) GENITOURINARY
    A) Kidney damage was observed in animals.
    0.2.14) DERMATOLOGIC
    A) Irritation and defatting of the skin may occur.
    0.2.20) REPRODUCTIVE
    A) Fertility was reduced in male rats and gerbils following daily ingestions of cyclohexanol.

Laboratory Monitoring

    A) Monitor kidney, liver, and cardiac function.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Emesis is NOT indicated due to risk of CNS depression.
    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) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    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.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) TLV-TWA - 50 ppm (200 mg/m(3))

Clinical Effects

Summary Of Exposure

    A) Exposure may occur by inhalation, ingestion, or percutaneous routes. Data on toxic effects in humans are limited. Cyclohexanol is an eye, nose, throat, and skin irritant. Central nervous system depression may occur.
    B) Signs and symptoms of exposure may include seizures, ataxia, lacrimation, corneal necrosis, salivation, nausea, vomiting, and diarrhea. Kidney, liver, and vascular injury and myocardial necrosis have been reported in experimental animals.

Vital Signs

    3.3.3) TEMPERATURE
    A) HYPOTHERMIA
    1) Following daily dermal applications of cyclohexanol, for 10 consecutive days, hypothermia was reported in rabbit studies (HSDB , 2002).

Heent

    3.4.1) SUMMARY
    A) Conjunctivitis, lacrimation, and irritation of mucous membranes may occur.
    3.4.3) EYES
    A) Eye irritation with corneal necrosis may occur, particularly following prolonged exposure to the vapor (ACGIH, 1991) Bingham et al, 2001; (HSDB , 2002).
    B) LACRIMATION may be noted (ACGIH, 1991) Grant & Schuman, 1993). Lacrimation has been reported in animal studies following dermal application of a soap containing cyclohexanol (no vapor exposure) (HSDB , 2002).
    3.4.5) NOSE
    A) Nasal irritation may occur (ACGIH, 1991).
    3.4.6) THROAT
    A) Throat irritation has been noted (ACGIH, 1991).
    B) SALIVATION may occur (ACGIH, 1991).

Cardiovascular

    3.5.1) SUMMARY
    A) Myocardial necrosis was observed in animals.
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NECROSIS ISCHEMIC
    a) Myocardial necrosis was reported in animals following a lethal dose (Proctor & Hughes, 1978).
    2) HYPOTENSION
    a) Following an intravenous injection, a transient decrease in blood pressure was reported in rabbit studies (HSDB , 2000).

Neurologic

    3.7.1) SUMMARY
    A) Headache, tremor, and CNS depression may occur.
    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) Headache has been reported, particularly following prolonged exposure to the vapor (ACGIH, 1991; HSDB , 2002).
    B) CENTRAL NERVOUS SYSTEM DEFICIT
    1) CNS depression and ataxia have occurred with short-term over exposure (ACGIH, 1991).
    C) DISORDER OF AUTONOMIC NERVOUS SYSTEM
    1) CASE SERIES - In a 2-year study of 453 workers who were exposed daily to less than the "permitted" concentrations of cyclohexanol, 114 workers showed nonspecific autonomic nervous system disturbances. In the non-exposed control group, 8/110 workers had similar disturbances (ACGIH, 1991).
    2) Marginally excessive human exposure may result in conjunctival irritation and headache, and there is a report of nonspecific disturbances of the autonomic nervous system (Clayton & Clayton, 1994).
    D) TREMOR
    1) Tremor may be noted following a toxic inhalation of the vapor (ITI, 1995; Gosselin et al, 1984; HSDB , 2002).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CNS DEPRESSION
    a) Oral exposure in rabbits to lethal concentrations (greater than 2.6 grams per kilogram) has resulted in tremors and seizures followed by CNS depression and loss of reflexes (HSDB , 2000).
    2) SEIZURES
    a) Following oral administration, cyclohexanol has caused seizures with less than lethal doses in animal studies. Following inhalation, mild seizures have resulted (HSDB , 2000).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea and vomiting have been reported.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) Nausea, vomiting and salivation may occur (ITI, 1985). Nausea may be prominent following acute vapor inhalation (HSDB , 2002).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) DIARRHEA
    a) Diarrhea has been reported in animal studies following oral administration of cyclohexanol (HSDB , 2000).

Hepatic

    3.9.1) SUMMARY
    A) Liver damage was observed in animals.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOCELLULAR DAMAGE
    a) Liver damage has been reported in animal studies (Plunkett, 1976; Sax, 1984; HSDB , 2000).

Genitourinary

    3.10.1) SUMMARY
    A) Kidney damage was observed in animals.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NEPHROPATHY TOXIC
    a) Kidney damage has been reported in animal studies (Plunkett, 1976; Sax, 1984; HSDB , 2000).

Dermatologic

    3.14.1) SUMMARY
    A) Irritation and defatting of the skin may occur.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Repeated long term skin exposure may produce irritation and defatting of the skin (ACGIH, 1989).
    3.14.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SKIN ULCERATION
    a) In a rabbit study, repeated dermal applications for 10 days, resulted in exudative ulceration and thickening of the skin in the area of contact (HSDB , 2000). Temporary erythema and superficial sloughing of the skin was noted in rabbits following daily application for 10 days of a 15% ointment (HSDB , 2000).

Reproductive

    3.20.1) SUMMARY
    A) Fertility was reduced in male rats and gerbils following daily ingestions of cyclohexanol.
    3.20.5) FERTILITY
    A) FERTILITY DECREASED MALE
    1) Fertility was reduced in male rats and gerbils following daily ingestions of cyclohexanol, 15 mg/kg, for 21 to 37 days (HSDB , 2002).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS108-93-0 (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

Genotoxicity

    A) When tested in several strains of Salmonella typhimurium, cyclohexanol was NOT mutagenic in concentrations of 500 mcg/plate, either in the presence or absence of a rat liver homogenate activation system (HSDB , 2002).
    B) A cytogenetic effect was reported in human leukocyte cells with a cyclohexanol dose of 100 mcmol/L (RTECS, 2002).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor kidney, liver, and cardiac function.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Monitor kidney and liver function in substantial exposure or in patients with previous kidney or liver disease.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor cardiac function in substantial exposure or in patients with previous cardiac disease.
    b) Following a significant oral or inhalational exposure, monitor patients for seizures or CNS depression.

Methods

    A) CHROMATOGRAPHY
    1) Cyclohexanol may be detected in urine samples using hydrolysis and gas chromatography with a flame ionization detector. A correlation of 0.88 was found between environmental cyclohexanone and cyclohexanol in urine using this method (Ong et al, 1991).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Monitor kidney, liver, and cardiac function.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) DILUTION -
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    B) EMESIS/ NOT RECOMMENDED -
    1) Emesis is not indicated due to risk of CNS depression.
    C) ACTIVATED CHARCOAL -
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS
    1) Is not indicated due to risk of CNS depression.
    B) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    C) ACTIVATED CHARCOAL
    1) 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).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive. There is no specific antidote.
    B) MONITORING OF PATIENT
    1) Kidney and liver damage has been observed in animals. Monitor kidney and liver functions.
    2) Cardiac monitoring may be indicated in patients with previous cardiac disease.
    3) Although only seen in animal studies following near lethal doses, patients should be monitored for seizures and CNS depression after ingestion or inhalation of massive amounts.
    C) 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, 2010; 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).

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.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

Summary

    A) TLV-TWA - 50 ppm (200 mg/m(3))

Minimum Lethal Exposure

    A) ADULT
    1) The minimum lethal human dose to this agent has not been delineated.
    2) Human volunteers reported eye, nose, and throat irritation when exposed to 100 ppm cyclohexanol for 3-5 minutes. Human subjects also showed erythema or edema after a 48-hour patch test using 4% cyclohexanol in petrolatum, but did not show irritation or sensitization. Based on animal data, it is expected that high concentrations of cyclohexanol will produce narcosis in humans (ACGIH, 1991; Clayton & Clayton, 1994; Grant, 1993; Hathaway et al, 1996) Synder, 1987).

Maximum Tolerated Exposure

    A) ADULT
    1) The maximum tolerated human exposure to this agent has not been delineated.
    2) 114 people in a group of 453 (25%) reported nonspecific autonomic nervous system disturbances after daily exposure to permissible concentrations of cyclohexanol for 2 years; only 8 out of 100 people in a control group reported similar disturbances (ACGIH, 1991) Synder, 1987).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) No data are available.

Workplace Standards

    A) ACGIH TLV Values for CAS108-93-0 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Cyclohexanol
    a) TLV:
    1) TLV-TWA: 50 ppm
    2) TLV-STEL:
    3) TLV-Ceiling:
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Skin
    3) Definitions:
    a) 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): Eye irr; CNS impair
    d) Molecular Weight: 100.16
    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 CAS108-93-0 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Cyclohexanol
    2) REL:
    a) TWA: 50 ppm (200 mg/m(3))
    b) STEL:
    c) Ceiling:
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: [skin]
    1) Indicates the potential for dermal absorption; skin exposure should be prevented as necessary through the use of good work practices and gloves, coveralls, goggles, and other appropriate equipment.
    f) Note(s):
    3) IDLH:
    a) IDLH: 400 ppm
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS108-93-0 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Cyclohexanol
    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: Cyclohexanol
    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 CAS108-93-0 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Cyclohexanol
    2) Table Z-1 for Cyclohexanol:
    a) 8-hour TWA:
    1) ppm: 50
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 200
    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: Lewis, 2000 RTECS, 2002)
    1) LD50- (INTRAMUSCULAR)MOUSE:
    a) 1 g/kg
    2) LD50- (INTRAPERITONEAL)MOUSE:
    a) 1352 mg/kg
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 2480 mg/kg (Lewis, 2000)
    4) LD50- (ORAL)RAT:
    a) 2060 mg/kg (Lewis, 2000)
    b) 1400 mg/kg -- General depressed activity; changes in lung, thorax or respiration; weight loss or decreased weight gain
    5) TCLo- (INHALATION)HUMAN:
    a) 75 ppm -- conjunctive irritation and other changes in sense organs and special senses

Pharmacology Toxicology

Toxicologic Mechanism

    A) Cyclohexanol is an eye, nose, throat, and skin irritant (Plunkett, 1976) Grant & Schuman, 1993). It is markedly irritating to the eyes, but only slightly irritating to the skin (Bingham et al, 2001).
    B) In animal studies, cyclohexanol has been shown to have a low order of acute oral and inhalational toxicity. Excessive inhalation exposure has been shown to be irritating to eyes, nose and throat and has resulted in narcosis (Bingham et al, 2001; (Clayton & Clayton, 1994; CHRIS , 1985).

Physicochemical

Physical Characteristics

    A) Cyclohexanol exists as a hygroscopic, viscous, colorless liquid or a sticky, colorless solid. Its odor has been described as camphor-like or menthol-like (AAR, 2000; ACGIH, 1991; Ashford, 2001) Bingham et al, 2001; (Budavari, 1996) Hathaway, 1996; (Lewis, 2000; Lewis, 2001; Verschueren, 1983).

Ph

    1) No information found at the time of this review.

Molecular Weight

    A) 100.18

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