BUPRENORPHINE

Buprenorphine is indicated to control moderate-to-severe pain (Prod Info Buprenex(R), 2001). It is a Schedule III narcotic under the Controlled Substance Act (Prod Info Suboxone(R), 2002; Prod Info Subutex(R), 2002).
Buprenorphine/naloxone and buprenorphine sublingual tablets are used to treat opioid dependence (Prod Info Suboxone(R), 2002; Prod Info Subutex(R), 2002).
Although buprenorphine transdermal system (Transtec(R)) is not available in the US, it is available in other countries (eg; Belgium, UK, Germany, New Zealand). It is used to treat moderate to severe cancer pain and severe chronic pain unresponsive to nonopioid analgesics (Evans & Easthope, 2003).
Buprenorphine has been abused by crushing the tablets and snorting the powder (Strang, 1991).
Several authors have reported that intravenous injection of crushed tablets may appear to be a major risk factor for fatalities (Boyd et al, 2003; Kintz, 2002; Kintz, 2001; Tracqui et al, 1998a).

FORMS

Buprenorphine is available as a 0.3 mg/mL solution for injection (Prod Info Buprenex(R), 2001).
Buprenorphine and naloxone combination formulation (Suboxone(R)/Reckitt Benckiser) is available as 2 mg/0.5 mg and 8 mg/2 mg sublingual tablets (Prod Info Suboxone(R), 2002).
Buprenorphine (Subutex(R)/Reckitt Benckiser) is available as 2 mg and 8 mg sublingual tablets (Prod Info Subutex(R), 2002).
Although buprenorphine transdermal system (Transtec(R)) is not available in the US, it is available in other countries (eg; Belgium, UK, Germany, New Zealand) (Evans & Easthope, 2003).
A recent open-label trial suggests that IM depot injections of buprenorphine (a novel polymer microcapsule formulation) may be clinically useful. This is not yet available commercially (Sobel et al, 2004).

SOURCES

Buprenorphine is a semisynthetic lipophilic opioid derivative of thebaine (Jasinski et al, 1978).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Schedule III prescription medication used for opioid addiction maintenance therapy.

PHARMACOLOGY: Partial agonist at the mu-opioid receptor, antagonist at the kappa opioid receptor.

TOXICOLOGY: The toxicity is an extension of the pharmacology. Effects include CNS depression, respiratory depression, constipation, and euphoria. Hypotension can occur from mast cell G protein activation and subsequent degranulation of histamine-containing vesicles.

EPIDEMIOLOGY: Buprenorphine exposures are common. In adults, severe toxicity may occur from crushing and injecting tablets, but is not common after ingesting buprenorphine alone. Children are at risk for toxicity following ingestion of less than a single tablet. While most deaths are due to overdose, deaths following inadvertent ingestion have occurred.

WITH POISONING/EXPOSURE

MILD TO MODERATE POISONING: Miosis, sedation, and relative bradycardia. Hepatitis is reported rarely.
SEVERE POISONING: CNS depression, coma, respiratory depression, and hypotension. Children, in particular, may develop profound, recurrent, or delayed CNS and respiratory depression. In adults, severe effects are generally only seen after crushing and injecting tablets, or after very large ingestions. Acute renal failure is reported rarely.

WITH THERAPEUTIC USE

Sedation, headache, nausea, vomiting, abdominal pain, constipation, and withdrawal syndrome. At high doses, buprenorphine's agonist effects plateau ("ceiling effect"), limiting the maximum analgesic and respiratory depressant effects. Due to this "ceiling effect," patients who are chronic users/abusers of opioids can experience withdrawal after ingestion of buprenorphine.

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

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

Prehospital decontamination is not recommended because of the potential for CNS depression.

-RANGE OF TOXICITY

MINIMUM LETHAL EXPOSURE

Several authors have suggested that intravenous injection of crushed tablets, a concomitant intake of psychotropic medications (especially benzodiazepines), and the high dosage of the buprenorphine formulation available (in spite of a theoretical 'ceiling effects') appear to be the major risk factors for fatalities (Boyd et al, 2003; Kintz, 2002; Kintz, 2001; Tracqui et al, 1998a).

MAXIMUM TOLERATED EXPOSURE

ADULTS

CASE REPORT: Following the intentional ingestion of 40 milligrams buprenorphine, a 35-year-old heroin-dependent man developed severe opioid withdrawal which was precipitated within one hour. In an attempt to alleviate symptoms, the patient took an additional 24 milligrams, with no relief, followed by another 16 or 24 milligrams. The patient was admitted to the hospital 2 days later and put on methadone therapy (Clark et al, 2002).
CASE REPORT: Severe hepatitis associated with acute renal failure and anuria have been reported in a patient following the ingestion (oral instead of sublingual) of 112 mg of buprenorphine. The buprenorphine and norbuprenorphine plasma levels were 224 ng/mL and 30 ng/mL, respectively. The patient recovered following the discontinuation of buprenorphine therapy and hemodialysis treatment (Houdret et al, 1999).
CASE REPORT: A 71-year-old woman developed nausea and vomiting, somnolence, miosis, and respiratory depression (8 breaths/minute, O2 saturation 68%) after applying 4 transdermal 52.5 mcg/hr buprenorphine patches at the same time. Each patch contained 30 mg buprenorphine. After repeated administration of naloxone 0.8 mg (total of 3 doses IV and 2 doses subcutaneously), the patient completely recovered (Magdalan & Merwid-Lad, 2008).
PROSPECTIVE STUDY: A prospective study was conducted to evaluate withdrawal symptoms in patients receiving buprenorphine 72 mg (3-fold the recommended daily dose of 24 mg) orally in an outpatient setting. Nine patients, who were at least 20 years of age, with opioid dependence and a history of opioid use for at least 1 year prior to maintenance treatment, were recruited into the study. Seven of the 9 patients completed the study. Patients were administered 72 mg (9 8-mg tablets) of buprenorphine on day 1 of the study. Blood samples were drawn 2, 24, 48, and 72 hours after ingestion, and opiate withdrawal symptoms were assessed, over a 72-hour period, with objective and subjective opiate withdrawal scales. Mean peak plasma concentrations of buprenorphine and norbuprenorphine (the metabolite) occurred 2 hours post-ingestion as expected and exhibited a gradual decline thereafter. Low withdrawal symptom scores from both the objective and subjective opiate withdrawal scales were reported in all 7 patients, and there were no significant adverse effects reported, indicating that high-dose buprenorphine was well-tolerated; however, further investigation is warranted (Hvittfeldt et al, 2015).

PEDIATRIC

CASE SERIES: CNS and respiratory depression (in one case, a respiratory rate of 2 per minute was observed) developed in 5 toddlers (age range 16 to 22 months) after ingestion of 8 to 10 mg buprenorphine. Recurrent respiratory depression as long as 18 hours after ingestion developed in one patient (Geib et al, 2006).
CASE REPORT: A 9-month-old developed miotic pupils, lethargy and respiratory depression after ingesting buprenorphine 8 mg/naloxone 2 mg. Effects reversed only after 5 mg naloxone IV. Mental status returned to normal 43 hours after ingestion (Cho et al, 2006).
CASE REPORT: Restlessness and bilateral miosis were reported in a 4-year-old child approximately 15 minutes after she ingested 4 mg of buprenorphine (one-half of an 8-mg tablet). She received activated charcoal, was observed for 24 hours, and never developed respiratory or CNS depression (Gaulier et al, 2004).
CASE SERIES: According to a retrospective review of buprenorphine overdoses involving children less than 6 years of age, Ingestion of 4 mg (one-half of a single 8 mg tablet; 0.215 mg/kg) caused CNS and respiratory depression in a 20-month-old boy, and ingestion of up to 24 mg of buprenorphine in a 2-year-old boy resulted in coma and respiratory depression. In the same review, a 20-month-old boy ingested 12 mg of buprenorphine and subsequently developed cyanosis, respiratory depression, and lethargy (Hayes et al, 2008).
CASE SERIES/CHILDREN: According to a retrospective case review of pediatric unintentional buprenorphine/naloxone exposures (n=9), drowsiness/lethargy, respiratory depression, agitation/irritability, vomiting, miosis, diaphoresis, and confusion occurred in children less than 3 years of age following ingestion of buprenorphine/naloxone tablets, at doses ranging from 0.07 to 0.41 mg/kg (Pedapati & Bateman, 2011).
CASE REPORT: A 2-year-old child became comatose (Glasgow Coma Scale (GCS) score of 5) with a fever (38.6%), hypertonia, and hyperreflexia after a suspected unintentional ingestion of 2 mg of buprenorphine (one-half of a 4-mg tablet). A brain CT scan without contrast was normal; however, a brain MRI revealed bilateral and symmetrical hypointense signals and hyperintense signals on T1 and T2 weighted images, respectively, with injuries in the white matter of the cerebral hemispheres and the cerebellum. The toxicology screen, obtained on hospital day 4, was positive for buprenorphine. With supportive care, the patient gradually recovered with a GCS score of 15 and a normal EEG, and was subsequently discharged on hospital day 8 (Bellot et al, 2011).

Carcinogenicity Ratings for CAS52485-79-7 :

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 CAS52485-79-7 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

LD50- (INTRAPERITONEAL)MOUSE:
- 90 mg/kg (RTECS, 2003)
LD50- (INTRAVENOUS)MOUSE:
- 24 mg/kg (RTECS, 2003)
LD50- (ORAL)MOUSE:
- 260 mg/kg (RTECS, 2003)
LD50- (INTRAPERITONEAL)RAT:
- 197 mg/kg (RTECS, 2003)
LD50- (INTRAVENOUS)RAT:
- 31 mg/kg (RTECS, 2003)

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS52485-79-7 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS52485-79-7 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS52485-79-7 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS52485-79-7 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS52485-79-7 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS52485-79-7 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS52485-79-7 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS52485-79-7 (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 CAS52485-79-7 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS52485-79-7 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS52485-79-7 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS52485-79-7 (EPA, 2005):

Not Listed

LABELS

NFPA

NFPA Hazard Ratings for CAS52485-79-7 (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 52485-79-7.

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 CAS52485-79-7 (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 CAS52485-79-7 (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 CAS52485-79-7 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS52485-79-7 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS52485-79-7 (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 CAS52485-79-7 (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

BUPRENORPHINE: 467.6 (Prod Info BUTRANS(R) transdermal system patch, 2014)

BUPRENORPHINE HYDROCHLORIDE: 504.1 (Prod Info BELBUCA(TM) buccal film, 2015; Prod Info buprenorphine HCl sublingual tablets, 2014)

DESCRIPTION/PHYSICAL STATE

BUPRENORPHINE: White or almost white powder; freely soluble in acetone; soluble in methanol and ether; slightly soluble in cyclohexane; very slightly soluble in water; pKa of 8.5; melting point: approximately 217 degrees C (Prod Info BUTRANS(R) transdermal system patch, 2014)

BUPRENORPHINE HYDROCHLORIDE: White or off-white powder; freely soluble in methanol; soluble in alcohol; sparingly soluble in water; practically insoluble in cyclohexane (Prod Info buprenorphine HCl sublingual tablets, 2014)

BUPRENORPHINE HYDROCHLORIDE: 3 to 7 (solution) (Prod Info buprenorphine HCl intramuscular injection solution, intravenous injection solution, 2009)

FREEZING/MELTING POINT

MELTING POINT

BUPRENORPHINE: Approximately 217 degrees C (Prod Info BUTRANS(R) transdermal system patch, 2014)

-REFERENCES

GENERAL BIBLIOGRAPHY

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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.

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Classification | Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents