PROPOFOL AND RELATED AGENTS

Propofol is a short-acting anesthetic given intravenously for the induction and maintenance of general anesthesia in both adults and children and for sedation in adults undergoing diagnostic procedures and in ventilated adults requiring intensive care (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008).
Fospropofol, a prodrug of propofol, is used intravenously for monitored anesthesia care sedation in adults undergoing diagnostic and therapeutic procedures. Its use in pediatric patients has not been determined (Prod Info LUSEDRA(R) IV injection, 2008).
RECREATIONAL ABUSE: Propofol has been used as an intravenous drug of abuse (Roussin et al, 2006; Odell, 1999). Its abuse by health care providers (ie, nurses, doctors ) has been reported numerous times in the medical literature (Roussin et al, 2006; Han et al, 2013). More recently, it has been abused among celebrities and other individuals (Han et al, 2013)

In 2011, due to the prevalence of propofol abuse, Korea regulated the substance as a psychotropic agent (Han et al, 2013).

FORMS

Propofol is available in 20 mL, 50 mL, and 100 mL vials as a 10 mg/mL solution in an injectable emulsion (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008).
Fospropofol is available in 35 mg/mL (a total of 1050 mg/30 mL) as a single-use, aqueous, clear, colorless solution in glass vials for intravenous use (Prod Info LUSEDRA(R) IV injection, 2008).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Propofol is used both for the induction and maintenance of general anesthesia. It also has several off-label uses including: conscious sedation, postoperative nausea and vomiting, and refractory status epilepticus and delirium tremens. There has also been documented recreational use, mostly involving medical professionals.

PHARMACOLOGY: Its mechanism of action is not well-defined, but it is thought to decrease the excitatory effects of glutamate.

TOXICOLOGY: Its toxic effects are secondary to its action as a general anesthetic.

EPIDEMIOLOGY: Significant toxicity is extremely rare, with case reports of death usually secondary to illicit use.

WITH POISONING/EXPOSURE

OVERDOSE: Propofol toxicity only occurs following IV injection. Overdose produces unconsciousness, respiratory depression and may cause hypotension and cardiovascular toxicity.

WITH THERAPEUTIC USE

ADVERSE EFFECTS: A "propofol infusion syndrome" has been described in patients receiving prolonged propofol sedation in the intensive care setting. This syndrome is characterized by metabolic acidosis, bradydysrhythmias, rhabdomyolysis, hyperkalemia, dyslipidemia, acute renal failure, massive ketonuria, elevated transaminases, fatty liver, myocardial failure and death. While most cases have involved children, it has been reported in adults as well.
OTHER: Other significant adverse reactions include hypotension, increased movement, local injection site burning, stinging, or pain and apnea. More rarely, there have been reports of hypertension in children, dysrhythmias, bradycardia, decreased cardiac output (especially with concurrent opioid use), tachycardia, pruritus, rash, hypertriglyceridemia, and respiratory acidosis during weaning.
RARE: Very rarely there are reports of events by the following individual organ systems: CARDIAC: cardiac arrest, asystole, syncope, dysrhythmias (ie, atrial and ventricular premature contractions); NEURO: postoperative unconsciousness, somnolence, delirium, dizziness, anticholinergic syndrome, agitation, hypertonia, and myoclonia; IMMUNE: anaphylaxis/anaphylactoid reaction, laryngospasm; RESPIRATORY: decreased lung function, hypoxia, cough, pulmonary edema, wheezing; GASTROINTESTINAL: nausea, pancreatitis, hypersalivation; MUSCULOSKELETAL: myalgia, rhabdomyolysis; EYE: vision abnormalities (ie, amblyopia); GENITOURINARY: discoloration of urine (green); DERMAL: extravasation, phlebitis, discolored hair and nailbeds (green); GENERAL: fever, flushing, chills, extremity pain, hypomagnesemia.

Editor's Note: An ERG guide with information appropriate to this material does not exist.

ACUTE CLINICAL EFFECTS

SUMMARY

USES: Propofol is used both for the induction and maintenance of general anesthesia. It also has several off-label uses including: conscious sedation, postoperative nausea and vomiting, and refractory status epilepticus and delirium tremens. There has also been documented recreational use, mostly involving medical professionals.
PHARMACOLOGY: Its mechanism of action is not well-defined, but it is thought to decrease the excitatory effects of glutamate.
TOXICOLOGY: Its toxic effects are secondary to its action as a general anesthetic.
EPIDEMIOLOGY: Significant toxicity is extremely rare, with case reports of death usually secondary to illicit use.

THERAPEUTIC

ADVERSE EFFECTS: A "propofol infusion syndrome" has been described in patients receiving prolonged propofol sedation in the intensive care setting. This syndrome is characterized by metabolic acidosis, bradydysrhythmias, rhabdomyolysis, hyperkalemia, dyslipidemia, acute renal failure, massive ketonuria, elevated transaminases, fatty liver, myocardial failure and death. While most cases have involved children, it has been reported in adults as well.
OTHER: Other significant adverse reactions include hypotension, increased movement, local injection site burning, stinging, or pain and apnea. More rarely, there have been reports of hypertension in children, dysrhythmias, bradycardia, decreased cardiac output (especially with concurrent opioid use), tachycardia, pruritus, rash, hypertriglyceridemia, and respiratory acidosis during weaning.
RARE: Very rarely there are reports of events by the following individual organ systems: CARDIAC: Cardiac arrest, asystole, syncope, dysrhythmias (atrial and ventricular premature contractions); NEUROLOGIC: Postoperative unconsciousness, somnolence, delirium, dizziness, anticholinergic syndrome, agitation, hypertonia, and myoclonia; IMMUNE: Anaphylaxis/anaphylactoid reaction, laryngospasm; RESPIRATORY: Decreased lung function, hypoxia, cough, pulmonary edema, wheezing; GASTROINTESTINAL: Nausea, pancreatitis, hypersalivation; MUSCULOSKELETAL: Myalgia, rhabdomyolysis; EYE: Vision abnormalities (ie, amblyopia); GENITOURINARY: Discoloration of urine (green); DERMAL: Extravasation, phlebitis, discolored hair and nailbeds (green); GENERAL: Fever, flushing, chills, extremity pain, and hypomagnesemia.

EXPOSURE

OVERDOSE: Propofol toxicity only occurs following IV injection. Overdose produces unconsciousness, respiratory depression and may cause hypotension and cardiovascular toxicity.

ACID BASE

METABOLIC ACIDOSIS: Propofol use and subsequent development of metabolic acidosis has occurred in multiple cases including both children and adults (Holzki et al, 2004; Parke et al, 1992; Cremer et al, 2001; Perrier et al, 2000). The acidosis often occurred concomitantly with bradydysrhythmias which necessitated pressor treatment.
INFUSION SYNDROME: Although rare, propofol infusion syndrome can occur and could be fatal in children who have received long-term propofol infusions. Clinical features have included: myocardial failure which are normally accompanied by bradydysrhythmias, acidosis, and renal failure (Wolf et al, 2001). Adults can also experience similar clinical effects, and fatalities have been reported (Smith et al, 2008; Perrier et al, 2000; Cremer et al, 2001).

CARDIOVASCULAR

HYPOTENSION: Intravenous propofol produces a dose-related degree of hypotension and decrease in systemic vascular resistance, which is not associated with a significant increase in heart rate or decrease in cardiac output (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008). Venodilation may contribute to propofol-mediated hypotension. Authors reported a mean decrease in systolic blood pressure of 30 mm Hg and a mean decrease in diastolic blood pressure of 11 mm Hg (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008). Several children have developed refractory hypotension associated with metabolic acidosis during prolonged propofol sedation (Cray et al, 1998; Hanna & Ramundo, 1998).
INFUSION SYNDROME: Propofol infusion syndrome is a rare event that can be fatal in both adult and pediatric critically ill patients who have received long-term propofol infusions. Clinical features of propofol infusion have included: myocardial failure which is often accompanied by bradydysrhythmias, metabolic acidosis, hyperkalemia, lipemia, hepatomegaly, rhabdomyolysis, and renal failure (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008).
BRADYCARDIA: Bradycardia has been reported following the use and propofol, and in a phase 4 study, bradycardia (heart rate less than 50 bpm) occurred in 4.8% of patients (Hug et al, 1993).
CARDIAC (BRADYDYSRHYTHMIAS) DYSRHYTHMIAS: Cardiac conduction dysrhythmias have been reported in multiple cases following propofol exposure (Strickland & Murray, 1995; Hanna & Ramundo, 1998; Cray et al, 1998), and progressive complications may include hemodynamic instability (Withington et al, 2004) and even death (Perrier et al, 2000; Parke et al, 1992).
HEART FAILURE: Propofol use in specific cases has been associated with eventual heart failure which was often preceded by metabolic acidosis and bradydysrhythmias (Parke et al, 1992; Cremer et al, 2001; Holzki et al, 2004).
VENTRICULAR TACHYCARDIA: Cases of ventricular tachycardia have been reported following propofol use (Olmedo et al, 2000; Jayamaha & Dowdle, 1993).

DERMATOLOGIC

PRURITUS: Pruritus has been reported frequently with therapeutic use of fospropofol. In clinical trials, pruritus was reported in 16% to 28% of patients receiving standard or modified doses of fospropofol (Prod Info LUSEDRA(R) IV injection, 2008).

FLUID ELECTROLYTE

HYPERKALEMIA: Hyperkalemia has occurred following propofol use (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008) and has been documented in several pediatric exposures to prolonged propofol infusions usually associated with metabolic acidosis and acute renal failure (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008; Strickland & Murray, 1995; Cray et al, 1998).

GASTROINTESTINAL

NAUSEA AND VOMITING: Nausea and vomiting can occur with therapeutic use of these agents (Prod Info LUSEDRA(R) IV injection, 2008; Prod Info DIPRIVAN(R) IV injectable emulsion, 2008).
SERUM AMYLASE ELEVATION: Cases of serum amylase elevations have been reported in patients receiving propofol therapy (Possidente et al, 1998; Cray et al, 1998), and this included one pediatric (10-month old) case receiving the drug for intensive care sedation (Cray et al, 1998).
PANCREATITIS: Pancreatitis was reported in a young adult following a single dose of propofol (Jawaid et al, 2002) and another young adult (a nurse anesthetist) was found dead with evidence of hemorrhagic pancreatitis at autopsy following chronic abuse of propofol (Jawaid et al, 2002).

GENITOURINARY

INFUSION SYNDROME: Acute renal failure has developed rarely in both adults and children who developed refractory hypotension and metabolic acidosis associated with prolonged propofol infusions (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008; Strickland & Murray, 1995; Wolf et al, 2001).
URINE DISCOLORATION: Discolored urine (olive green, rusty brown, tea-colored) has been reported in several pediatric exposures to prolonged propofol infusions used for intensive care sedation (Cray et al, 1998; Hanna & Ramundo, 1998).
KETONURIA: Severe ketonuria developed in a 12-year-old girl with a traumatic brain injury requiring prolonged propofol sedation (total 59 hours) to decrease agitation and unstable intracranial hypertension (Canivet et al, 1994).
MYOGLOBINURIA: Myoglobinuria and an elevated creatine kinase were reported in a toddler requiring a prolonged propofol infusion for sedation (Cray et al, 1998).

HEENT

EXTERNAL OPHTHALMOPLEGIA: Complex external ophthalmoplegia has been reported in patients recovering from propofol anesthesia (Marsch & Schaefer, 1994).
DECREASED INTRAOCULAR PRESSURE: During anesthesia with propofol, a transient decrease in intraocular pressure has been reported (Guedes et al, 1988; Vanacker et al, 1987).
LARYNGEAL SWELLING: Two cases of life-threatening submandibular and laryngeal swelling with airway compromise have been reported (Couldwell et al, 1993).

HEMATOLOGIC

HYPERLIPIDEMIA: Hyperlipemia has occurred following prolonged, high dose infusions (greater than 5 mg/kg/hr for greater than 48 hours), but may also occur following a large dose or short-term therapy. It has been observed as part of the constellation of symptoms associated with propofol infusion syndrome (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008).
PORPHYRIA: A patient with acute intermittent porphyria undergoing propofol anesthesia developed elevated porphyrins postoperatively (Elcock & Norris, 1994).

HEPATIC

STEATOSIS: Hepatic steatosis has been reported in several children who developed metabolic acidosis, refractory hypotension and dysrhythmias while receiving prolonged propofol sedation (Parke et al, 1992).

IMMUNOLOGIC

ANAPHYLAXIS: There have been rare reports of anaphylaxis with propofol use, with angioedema, bronchospasm, erythema, and hypotension observed during these events (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008). Anaphylactic shock has also been reported (McHale & Konieczko, 1992; De Leon-Casasola et al, 1992).

MUSCULOSKELETAL

INFUSION SYNDROME: Rhabdomyolysis has occurred following prolonged, high dose infusions (greater than 5 mg/kg/hr for greater than 48 hours), but may also occur following a large dose or short-term therapy. It has been observed as part of the constellation of symptoms associated with propofol infusion syndrome (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008).

NEUROLOGIC

CNS EXCITATION: In a review of 1465 patients, 14% had some manifestations of excitation. Symptoms included: twitching, tremor, hypertonus, masseter spasm, and hiccups (Stark et al, 1985).
SEIZURE: Propofol may have both anticonvulsant and proconvulsant properties, and there have been at least 50 reports of seizure activity following propofol use (Sutherland & Burt, 1994). Additionally, seizures have been reported in patients with and without a prior history of seizure disorder (Hickey et al, 2005; Gildar, 1993; Hendley, 1990).
PARESTHESIA: Paresthesia described as pain, burning or stinging sensation has been reported frequently in patients undergoing minor procedures who received a standard or modified dose of fospropofol. Up to 74% of patients reported some type of paresthesia (Prod Info LUSEDRA(R) IV injection, 2008).
HYPERREFLEXIA: Hyperreflexia, opisthotonus, and hypertonicity have been reported (DeFriez & Wong, 1992; Saunders & Harris, 1990).

RESPIRATORY

APNEA: Apnea is common with administration of these agents, as would be expected with this type of anesthetic agent (Prod Info LUSEDRA(R) IV injection, 2008; Prod Info DIPRIVAN(R) IV injectable emulsion, 2008). In one study induction of anesthesia with 2 mg/kg caused apnea in 48% of the patients with a mean duration of 51 seconds (Gepts et al, 1985).
BRONCHOSPASM: In patients with hyperreactive airway disease, bronchospasm has been described in several reports (Pedersen, 1992).

VITAL SIGNS

FEVER: Fever has been associated with prolonged propofol infusion (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008; Plotz et al, 1997; Olmedo et al, 2000).

CHRONIC CLINICAL EFFECTS

WITH POISONING/EXPOSURE

Propofol has abuse potential (Roussin et al, 2006; Follette & Farley, 1992).
Propofol is a sensitizer. There are several cases of anaphylactic shock reported in the literature (Laxenaire et al, 1988; McHale & Konieczko, 1992; De Leon-Casasola et al, 1992). Some of these patients had never received propofol prior to the anaphylactic reaction, suggesting that significant cross-reactivity with other compounds may occur (Laxenaire et al, 1988).
Propofol would be predicted to cause allergic contact dermatitis with repeated skin exposure because of its known respiratory sensitization and structural similarity to related other antioxidants which are known to cause dermatitis (Bardazzi et al, 1988).

WITH THERAPEUTIC USE

When propofol is administered to patients for several days as a sedative, withdrawal symptoms consisting of confusion, tremors, hallucinations, and grand mal seizures can occur (Au et al, 1990; Grant & Worsley, 1991).
Propofol is a sensitizer. There are several cases of anaphylactic shock reported in the literature (Laxenaire et al, 1988; McHale & Konieczko, 1992; De Leon-Casasola et al, 1992). Some of these patients had never received propofol prior to the anaphylactic reaction, suggesting that significant cross-reactivity with other compounds may occur (Laxenaire et al, 1988).
Propofol would be predicted to cause allergic contact dermatitis with repeated skin exposure because of its known respiratory sensitization and structural similarity to related other antioxidants which are known to cause dermatitis (Bardazzi et al, 1988).

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

There is no role for GI decontamination as propofol toxicity only occurs during parenteral administration.

-RANGE OF TOXICITY

MINIMUM LETHAL EXPOSURE

SUMMARY

Long-term propofol infusions have resulted in fatalities in both children and adults. Propofol Infusion Syndrome is a rare entity that may develop after prolonged high dose propofol infusion and is characterized by: myocardial failure which is normally accompanied by bradydysrhythmias, metabolic acidosis, and renal failure (Prod Info DIPRIVAN(R) IV injectable emulsion, 2008; Perrier et al, 2000; Cremer et al, 2001; Wolf et al, 2001).

In a retrospective cohort analysis conducted over 4 years of 50 patients with severe traumatic brain injury administered a propofol infusion, 3 (6%) patients developed propofol infusion syndrome; 1 patient expired. Each patient developed symptoms at doses of less than or equal to 134 mcg/kg/min for a time period ranging from 85 to 135 hours, while receiving concomitant vasopressor (ie, phenylephrine, dopamine) therapy. The authors found that the concomitant use of propofol and vasopressors was associated with the development of propofol infusion syndrome (odds ratio 29, 95% CI 1.5-581). It was further suggested that propofol doses should not exceed 83 mcg/kg/min for more than a few days, as previously described in the literature (Smith et al, 2008).

Fospropofol, a prodrug of propofol, is used for monitored sedation in adults. Its safety in prolonged sedation has not been established (Prod Info LUSEDRA(R) IV injection, 2008).

CASE REPORTS

PEDIATRIC

Parke et al (1992) reported the onset of bradydysrhythmias along with metabolic acidosis early in the clinical course of 5 children who developed fatal myocardial failure after receiving propofol for intensive care sedation.
A 28-month-old received a 42 hour propofol infusion and developed metabolic acidosis, rhabdomyolysis and electrolyte dysfunction. Despite correction of the patient's electrolyte abnormalities, he died on postoperative day 3 after developing ventricular tachycardia that was unresponsive to therapy (Olmedo et al, 2000).
INTRA-ARTERIAL INJECTION/LACK OF EFFECT: A 10-year-old girl being prepped for surgery following a traumatic injury inadvertently received 50 mg (5 mL) of propofol via an intra-arterial line. It was noted that the arterial line appeared cloudy a short time later and the arterial waveform dampened. An attempt to remove the remaining fluid in the arterial line was made. The child was already intubated so it was difficult to assess if any pain was present in the extremity. However, vital signs remained normal. Surgery proceeded and the child reported no arm pain or paresthesia during the post operative period. Six-months later, there was no report of any functional changes or deficits (Shenoi et al, 2014).

ADULT

A 29-year-old woman radiographer died after self-administration of 400 mg of intravenous propofol (Baselt, 2004).
Five adult patients with head injuries had fatal cardiac arrests after propofol infusions for sedation. The events appeared similar to that described in children (ie, progressive myocardial failure, various cardiac dysrhythmias, metabolic acidosis, rhabdomyolysis, and hyperkalemia around the 4th or 5th day of sedation) (Cremer et al, 2001). Infusions of more than 5 mg/kg/hr appeared to be associated with an increased risk of developing propofol infusion syndrome.
An 18-year-old victim of an auto accident received a continuous infusion of propofol (50 mg/hr) for agitation, which was increased to a rate of 55 mg/hr following surgery for sedation. On hospital day 5, the patient developed a new onset of left bundle branch block with bradycardia and progressive metabolic acidosis. The patient then developed pulseless electrical activity, asystole and death, despite aggressive supportive care. Propofol had been infused for 98 hours at a rate of 530 to 700 mg/hr (Perrier et al, 2000).

MAXIMUM TOLERATED EXPOSURE

CASE REPORTS

ADULT

CHRONIC USE: A 30-year-old male resident anesthesiologist presented to an inpatient detoxification center after using propofol chronically (100 to 200 mg injections 20 to 40 times daily; maximum daily dose 4 g) for over a year. He didn't experience tolerance of the desired effects (cloudy and euphoric relaxation after a 100 mg dose and sleep induction after a 200 mg dose) despite the repeated propofol use. During the first 4 to 5 days after propofol discontinuation, he developed mild to moderate withdrawal symptoms (eg, feeling unreal, very sensitive to noise and light, muscle twitching, shaking or trembling, dizziness, feeling faint, feeling sick and depressed, loss of memory, and loss of appetite). He also developed craving symptoms that were more intense and lasted longer than the symptoms of withdrawal. After 2 weeks of abstinence, he was transferred to a 4-month inpatient rehabilitation treatment (Bonnet & Scherbaum, 2012).

CASE REPORTS

PEDIATRIC

A 6-month-old, 6.7 kg infant was scheduled for elective craniosynostosis repair and inadvertently received a 44.7 mg/kg/hr dose of propofol, a 10-fold overdose (intended dose 4.47 mg/kg/hr), over 4 hours. Approximately 3 hours after the infusion was started, the systolic BP dropped to 40 mmHg, heart rate remained at 100 BPM and central venous pressure increased to 12 cm H2O (4 cm H2O preoperative). Epinephrine (1 mcg) and dopamine were given. At 4 hours, the inadvertent overdose was recognized and the infusion was stopped. Once the heart rate and blood pressure stabilized, surgery resumed. The patient remained stable and was extubated uneventfully 24 hours after admission. Postoperatively the patient did well and was discharged to home, with no evidence of cardiac or neurologic deficits (Paterman et al, 2004).
A 10-month old developed first degree AV-block with right bundle branch block following a prolonged propofol infusion (total dose: 4370 mg over 50.5 hours). Despite progressing metabolic acidosis and hypoxia, clinical symptoms improved following continuous veno-venous hemofiltration (Cray et al, 1998).
A 2-year-old developed propofol infusion syndrome (ie, nodal bradycardia, oliguria, and metabolic acidosis) after receiving an infusion at an average hourly rate of 5.2 mg/kg over a 72 hour period. The infusion was stopped and the child was successfully treated with hemofiltration (Wolf et al, 2001).

Carcinogenicity Ratings for CAS2078-54-8 :

ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
EPA (U.S. Environmental Protection Agency, 2011): Not Listed
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
NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
MAK (DFG, 2002): Not Listed
NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

TOXICITY AND RISK ASSESSMENT VALUES

EPA IRIS

EPA Risk Assessment Values for CAS2078-54-8 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

ANIMAL DATA
- LD50- (INTRAVENOUS)MOUSE:
- LD50- (ORAL)MOUSE:
- LD50- (INTRAVENOUS)RAT:
- LD50- (ORAL)RAT:

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS2078-54-8 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS2078-54-8 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS2078-54-8 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS2078-54-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS2078-54-8 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS2078-54-8 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS2078-54-8 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS2078-54-8 (U.S. Environmental Protection Agency, 2010b):

Not Listed
Editor's Note: The D, F, and K series waste numbers and Appendix VIII to Part 261 -- Hazardous Constituents were not included. Please refer to 40 CFR Part 261.

EPA SARA Title III, Extremely Hazardous Substance List for CAS2078-54-8 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS2078-54-8 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS2078-54-8 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS2078-54-8 (EPA, 2005):

Listed as: Phenol, 2,6-bis(1-methylethyl)-

LABELS

NFPA

NFPA Hazard Ratings for CAS2078-54-8 (NFPA, 2002):

Not Listed

-PERSONAL PROTECTION

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

PROTECTIVE CLOTHING

CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 2078-54-8.

Specific recommendations and test data for this chemical were not found in the available manufacturers' product literature. A complete list of consulted manufacturers and references is presented below.

-PHYSICAL HAZARDS

FIRE HAZARD

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

FLAMMABILITY CLASSIFICATION

NFPA Flammability Rating for CAS2078-54-8 (NFPA, 2002):

Not Listed

FIRE CONTROL/EXTINGUISHING AGENTS

Editor's Note: An ERG guide with information appropriate to this material does not exist.

NFPA Extinguishing Methods for CAS2078-54-8 (NFPA, 2002):

Not Listed

EVACUATION PROCEDURES

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

AIHA ERPG Values for CAS2078-54-8 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS2078-54-8 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS2078-54-8 (National Research Council, 2010; National Research Council, 2009; National Research Council, 2008; National Research Council, 2007; NRC, 2001; NRC, 2002; NRC, 2003; NRC, 2004; NRC, 2004; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; United States Environmental Protection Agency Office of Pollution Prevention and Toxics, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 62 FR 58840, 1997; 65 FR 14186, 2000; 65 FR 39264, 2000; 65 FR 77866, 2000; 66 FR 21940, 2001; 67 FR 7164, 2002; 68 FR 42710, 2003; 69 FR 54144, 2004):

Not Listed

NIOSH IDLH Values for CAS2078-54-8 (National Institute for Occupational Safety and Health, 2007):

Not Listed

CONTAINMENT/WASTE TREATMENT OPTIONS

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

SMALL LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

LARGE LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

-PHYSICAL/CHEMICAL PROPERTIES

MOLECULAR WEIGHT

178.3 (RTECS , 2001)

-REFERENCES

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National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Germane (Proposed). United States Environmental Protection Agency. Washington, DC. 2008j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963906&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

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Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents