PHENOBARBITAL

C12-H12-N2-O3 (Prod Info phenobarbital oral tablets, 2006; Prod Info phenobarbital oral solution, 2005; Prod Info LUMINAL(R)SODIUM powder for IV injection, 2008)

ERG GUIDE NUMBER

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

USES/FORMS/SOURCES

USES

Phenobarbital is a long-acting barbiturate. It is used as a hypnotic, sedative, and anticonvulsant in treatment of grand mal epilepsy and focal cortical seizures. It is also used in veterinary medicine and as a laboratory reagent. Phenobarbital is a drug of abuse (HSDB, 1996; (Budavari, 1996).

FORMS

Phenobarbital occurs as an odorless white or clear, glistening crystalline solid with a slightly bitter taste (HSDB, 1996; (Lewis, 1993; Budavari, 1996). It is slightly acidic in a saturated water solution, with a pH of approximately 5 (HSDB, 1996). It is soluble in alcohol, chloroform, and in alkaline hydroxides and carbonates. It is slightly soluble in water and benzene (HSDB, 1996; (Lewis, 1993).
In contrast to the free acid, the sodium salt is very soluble in water and propylene glycol, is soluble in alcohol, is insoluble in chloroform, and is alkaline in solution (HSDB, 1996).
Commercial forms in the US include a USP powder, tablets of 8, 15, 25, 30, 60 and 100 mg, and elixirs containing 7.5 or 20 mg per 5 mL and 12 to 15% ETHANOL (HSDB, 1996). In cases of overdose of an elixir, possible contribution of ethanol to the overall toxicity should be taken into account. Ethanol may increase the CNS depression induced by phenobarbital.
The sodium salt of phenobarbital is available in injectable solution, which may contain PROPYLENE GLYCOL as solvent (HSDB, 1996). Propylene glycol may contribute to the toxicity of this formulation.
The sodium salt is unstable in water, and absorbs carbon dioxide from moist air to release phenobarbital (HSDB, 1996).
Some of the toxicologic literature on phenobarbital may not indicate whether the involved agent was the free acid or the sodium salt. The two substances would be expected to have similar pharmacologic effects. Distinctions between effects due to the free acid versus the sodium salt will be indicated in this review where known.

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

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

ACUTE CLINICAL EFFECTS

WITH POISONING/EXPOSURE

Phenobarbital is acutely toxic. Psychomotor slowing and intellectual deterioration may occur at serum levels between 15 to 20 mcg/mL, and levels above 40 mcg/mL are often associated with toxic symptoms (Reynolds & Travers, 1974; Hvidberg & Dam, 1976; Gallagher et al, 1973; AMA, 1992). A dose of 6 to 10 grams, corresponding to a blood concentration of 80 mcg/mL, is potentially fatal (HSDB, 1996; (Gilman et al, 1985).
Because most of the literature on phenobarbital refers to its use in long-term therapy, the distinction between true acute and chronic effects is difficult to establish. Many cases of acute overdose may be in chronic users or abusers of the drug.
Phenobarbital is a central nervous system depressant. Moderate overdoses resemble alcohol intoxication. It can cause nausea, vomiting, diarrhea and/or constipation (Prod Info Phenobarbital(R), 1993). In increasing doses, it may cloud perception and distort judgement, induce drowsiness, lethargy, dizziness, headache, ataxia, sleep and anesthesia, respiratory depression, hypothermia, coma, shock, and death from respiratory failure (HSDB, 1996; (Matthew & Lawson, 1966; Fincham & Schottelius, 1973).
Phenobarbital alters the stages of sleep (HSDB, 1996). Nightmares and night terrors can occur after exposure to phenobarbital for several nights, perhaps because of deprivation of rapid eye movement and/or stage 4 sleep (HSDB, 1996).
Early signs of phenobarbital intoxication include either slow or rapid, shallow breathing (HSDB, 1996). Respiratory depression may lead to metabolic acidosis and hypoxia (HSDB, 1996).
Phenobarbital can induce burst-suppression type abnormalities of the electroencephalogram, including short periods of inactivity (HSDB, 1996). Reflexes are depressed in relation to the severity of CNS depression, but deep reflexes may persist with coma (HSDB, 1996).
Hypotension develops from both a direct pharmacologic effect of phenobarbital and also as a secondary effect from hypoxia (Amitai & Degani, 1990; Pond et al, 1984).
The heart is a major target of the acute toxicity of phenobarbital. Contractility is depressed, and cardiac arrest may occur (Matthew & Lawson, 1966). A weak, rapid pulse occurs in shock.
The pupils may be constricted and reactive to light, and in late stages may be dilated from hypoxia (HSDB, 1996).
Hypothermia with cold, sweaty skin develops in the presence of shock (Matthew & Lawson, 1986).
The hematocrit may rise and renal ischemia may occur. Phenobarbital directly affects renal tubular transport at doses which produce deep anesthesia; both secretion and reabsorption can be inhibited (HSDB, 1996; (Gilman et al, 1985). Kidney failure can be a fatal complication of severe phenobarbital poisoning (HSDB, 1996).
Effects on the respiratory system include respiratory depression, pulmonary edema, atelectasis, and bronchopneumonia (HSDB, 1996; (Pond et al, 1984). A potentially fatal exfoliative dermatitis accompanied by fever, delirium, and degenerative changes in the liver has been associated with phenobarbital (HSDB, 1996).
Residual sedation, distortions of mood or judgement, and impaired motor skills may persist for hours after an acute overdose (HSDB, 1996).
"Barb burns" (blisters on the skin over pressure points) have occurred in up to 6.5% of cases of phenobarbital overdose; they usually appear within 24 hours of coma (Beveridge & Lawson, 1965).

WITH THERAPEUTIC USE

Phenobarbital is a long-acting barbiturate; its duration of action after an acute dose usually exceeds 6 hours (Anderson et al, 1976).
The usual dose as a sedative is 15 to 40 mg, 2 to 3 times per day; the average hypnotic dose is 100 to 200 mg for adults (HSDB, 1996; (Gilman et al, 1985). Onset of symptoms is 20 to 60 minutes after an oral dose (HSDB, 1996). Therapeutic doses of 1 to 5 mg/kg/day produce plasma levels in the range of 10 to 40 mcg/mL (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA, 1992).
Paradoxical excitement and hyperactivity can occur in children or geriatric or debilitated patients (HSDB, 1996; (Levenstein et al, 1984).
DRUG INTERACTION

Phenobarbital is a model inducer of cytochrome P-450 microsomal mixed function oxidase enzymes in the liver. Specifically, it induces cytochrome P4502B1, P4502B2, and P450E. These enzymes are involved in the metabolism of many xenobiotic compounds. Phenobarbital exposure may affect an individual's metabolism or sensitivity to other agents metabolized by this route.
Concurrent exposure to phenobarbital may DECREASE an individual's sensitivity to coumarin and digitoxin because of enhanced metabolism of the latter to inactive metabolites (HSDB, 1996).
Phenobarbital can decrease absorption of griseofulvin and increase metabolism of doxycycline (HSDB, 1996).
Other known interactions include acetophenetidin, urinary acidifying agents, actinomycin D, ethanol, alkalinizing agents, DL-amphetamine, androgens, androsterone, antihistamines, anti-inflammatory drugs, antipyrine, bishydroxycoumarin, carisoprodol, chloramphenicol, chlordiazepoxide, chlorpromazine, phenothiazines, phenylbutazone, procaine, puromycin, salicylates, sodium bicarbonate, steroids and oral contraceptives, sulfonamides, sulfonylureas, thyroxine, minor tranquilizers, and zoxazolamine (HSDB, 1996).
Other potential or proven interactions include DDT, desoxycorticosterone, dipyrone, hexobarbital, folic acid antagonists, hydantoins, hypnotics, monoamine oxidase inhibitors, meperidine, meprobamate, methylphenidate, nitrofurantoin, and phenacetin (HSDB, 1996).
Drugs whose elimination is enhanced by phenobarbital include: beta-adrenergic antagonists (metoprolol and propranolol), quinidine, sulfadimethoxine, testosterone, and tricyclic antidepressants (HSDB, 1996).
Phenobarbital enhances liver toxicity of chlorinated hydrocarbons (by promoting lipid peroxidation) (HSDB, 1996).
Many other interactions have been described.

ANIMAL STUDIES - Acute toxicity of phenobarbital has shown variation with seasons of the year in mice: maximum potency (with lethality as the endpoint) was seen in January, and the minimum was in July (Bruguerolle, 1988).

CHRONIC CLINICAL EFFECTS

WITH POISONING/EXPOSURE

Phenobarbital can be addictive and is a drug of abuse. Dependence can occur with a daily dose of 300 to 700 mg over one or two months, and addicts may take as much as a gram per day (doses 10 to 100 times HIGHER than the therapeutic dose).
Toxic and therapeutic doses of phenobarbital have been linked with clinical depression and thoughts of suicide (Barabas & Mathews, 1988; (Brent et al, 1987).
Chronic users or abusers of phenobarbital may have variable pupillary responses, most often with miosis, or with mydriasis in cases of severe intoxication. Chronic abusers may have ptosis (Abel & Gourley, 1983). Transient optic neuropathy has been reported in one case (Homma et al, 1989).

WITH THERAPEUTIC USE

Discontinuation of phenobarbital precipitates a withdrawal syndrome including nausea, vomiting, loss of appetite, nervousness, anxiety, weakness, tremors, grand mal convulsions, auditory and visual hallucinations, delirium, fever, and death (HSDB, 1996).
Phenobarbital has been reported to produce many kinds of neurological effects with long-term therapy. Other neurological effects include ataxia, dyskinesias (movement disorders), and seizures (Fincham & Schottelius, 1973; Chadwick, 1976). Phenobarbital can cause or exacerbate tics (HSDB, 1996; (Burd, 1986).
Some patients are hypersensitive to phenobarbital. Hypersensitive patients can rarely develop a potentially fatal pseudolymphoma from phenobarbital therapy. Signs and symptoms include lymphadenopathy, eosinophilia, fever, exfoliative dermatitis, and liver damage (HSDB, 1996).
Other symptoms of hypersensitivity include urticaria, angioedema, rash, serum sickness, erythema multiforme, and Stevens-Johnson syndrome (HSDB, 1996; (Roberts et al, 1990).
A fatal hypersensitivity reaction involving fulminant liver failure and massive liver necrosis occurred in a 2-year-old child who had received 2 mg/kg/day of phenobarbital for febrile seizures over a period of approximately 2 weeks (Mockli et al, 1989).
Blood disorders, including thrombocytopenic purpura, megaloblastic anemia, leukopenia, agranulocytosis, macrocytosis, and methemoglobinemia, are rare complications of long-term phenobarbital therapy (AMA, 1992) Gibson, 1966; (Eastham, 1975). Coagulation defects have been reported in newborns.
Long-term therapy with phenobarbital (greater than 6 months) can cause osteomalacia and hypocalcemia (Hahn, 1975) Anast, 1975; (Christiansen, 1973; Tolman, 1975; Ray & Rao, 1974; Andreasen, 1973; Anon, 1976; Mosekilde & Melsen, 1976; Mosekilde, 1972; Sherk, 1977; Hoikka et al, 1982), by reducing levels of 24,25-dihydroxyvitamin D (Zerwekh et al, 1982).
Chronic administration of phenobarbital can affect kidney function (Faarup & Christensen, 1974) Curtis, 1977). Liver toxicity may be part of a hypersensitivity reaction (Weisburst, 1976; Kahn & Faguet, 1984).
Connective tissue disorders, including frozen shoulder, arthralgias, and Peyronie's disease, were seen in 6% of patients treated with phenobarbital (or primidone) for at least 6 months (Mattson et al, 1989).

ANIMAL STUDIES - Phenobarbital can exhibit CUMULATIVE TOXICITY in dogs, with signs of incoordination, slowed mental reaction, and depression (HSDB, 1996).

-RANGE OF TOXICITY

MAXIMUM TOLERATED EXPOSURE

Carcinogenicity Ratings for CAS50-06-6 :

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): 2B ; Listed as: Phenobarbital

2B : The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.

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 CAS50-06-6 (U.S. Environmental Protection Agency, 2011):

Not Listed

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS50-06-6 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS50-06-6 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS50-06-6 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS50-06-6 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS50-06-6 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS50-06-6 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS50-06-6 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS50-06-6 (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 CAS50-06-6 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS50-06-6 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS50-06-6 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS50-06-6 (EPA, 2005):

Not Listed

LABELS

NFPA

NFPA Hazard Ratings for CAS50-06-6 (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 50-06-6.

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 CAS50-06-6 (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 CAS50-06-6 (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 CAS50-06-6 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS50-06-6 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS50-06-6 (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 CAS50-06-6 (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

Base: 232.24 (Prod Info phenobarbital oral tablets, 2006; Prod Info phenobarbital oral solution, 2005)

DESCRIPTION/PHYSICAL STATE

Phenobarbital is a white, crystalline, hygroscopic, odorless, slightly bitter powder (Prod Info LUMINAL(R)SODIUM powder for IV injection, 2008; Prod Info phenobarbital oral tablets, 2006; Prod Info phenobarbital oral solution, 2005).

Phenobarbital oral solution is soluble in alcohol, ether, and in solutions of fixed alkali hydroxides and carbonates; very slightly soluble in water; and sparingly soluble in chloroform (Prod Info phenobarbital oral solution, 2005). Phenobarbital tablets are freely soluble in alcohol or ether, soluble in chloroform, and slightly soluble in water (Prod Info phenobarbital oral tablets, 2006). Phenobarbital sodium solution for injection is readily soluble in water (Prod Info LUMINAL(R)SODIUM powder for IV injection, 2008).

Saturated solution: 5.6 (Prod Info phenobarbital oral tablets, 2006)

-REFERENCES

GENERAL BIBLIOGRAPHY

40 CFR 372.28: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Lower thresholds for chemicals of special concern. National Archives and Records Administration (NARA) and the Government Printing Office (GPO). Washington, DC. Final rules current as of Apr 3, 2006.

40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.

49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.

62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.

65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.

67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.

68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.

69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.

AIHA: 2006 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook, American Industrial Hygiene Association, Fairfax, VA, 2006.

AMA: Department of Drugs: AMA Evaluations Subscription, American Medical Association, Chicago, IL, 1992.

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Briggs GG, Freeman RK, & Yaffe SJ: Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 5th ed, Williams & Wilkins, Baltimore, MD, 1998, pp 843-48.

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Cornelissen M, Steegers-Theunissen R, & Kollee L: Increased incidence of neonatal vitamin K deficiency resulting from maternal anticonvulsant therapy. Am J Obstet Gynecol 1993; 168:923-928.

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