BUSULFAN AND RELATED AGENTS

Busulfan tablet is indicated as part of a conditioning regimen in combination with cyclophosphamide prior to allogenic hematopoietic progenitor cell transplantation in patients with chronic myelogenous leukemia. Busulfan injection in combination with cyclophosphamide is effective in conditioning regimens prior to bone marrow transplantation for various hematologic malignancies and non-malignant diseases (Prod Info BUSULFEX(R) intravenous injection, 2015; Prod Info MYLERAN(R) oral film coated tablets, 2011).
Treosulfan is used palliatively or as an adjunct to surgery primarily for the treatment of ovarian cancer (S Sweetman , 2000).

FORMS

Busulfan is available as 2 mg tablets and 60 mg in 10 mL vials (6 mg/mL) for intravenous injection (Prod Info BUSULFEX(R) intravenous injection, 2015; Prod Info MYLERAN(R) oral film coated tablets, 2011).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Busulfan is indicated as part of a conditioning regimen in combination with cyclophosphamide prior to allogenic hematopoietic progenitor cell transplantation in patients with chronic myelogenous leukemia.

PHARMACOLOGY: Busulfan is a bifunctional alkylating agent whose chemical structure consists of two labile methanesulfonate groups that are attached to opposite ends of a four carbon alkyl chain. Its cytotoxicity is related to the alkylation of DNA due to the production of reactive carbonium ions caused by the release of the methanesulfonate groups when busulfan is hydrolyzed in an aqueous medium.

EPIDEMIOLOGY: Exposure may occur; however, overdose is rare.

WITH POISONING/EXPOSURE

Busulfan overdose information is limited. Overdose effects are anticipated to be an extension of adverse effects at therapeutic doses. Alopecia nausea, vomiting, stomatitis, anorexia, and pancytopenia were reported in a 4-year-old child following a single dose ingestion of 140 mg. A total oral busulfan dose of 23.3 mg/kg was inadvertently administered to a 2-year-old child who survived without sequelae; however, an acute busulfan dose of 2.4 grams was fatal in a 10-year-old child.

WITH THERAPEUTIC USE

COMMON: Commonly reported adverse reactions, with an incidence of greater than 60%, include myelosuppression (ie, granulocytopenia, thrombocytopenia, anemia), nausea, vomiting, stomatitis, anorexia, diarrhea, abdominal pain, hypomagnesemia, hypokalemia, hyperglycemia, insomnia, fever, anxiety, and headache. Seizures, coma, and veno-occlusive liver disease have been associated, in children and adults, with high-dose therapeutic administration of busulfan.
INFREQUENT: Adverse effects, reported less frequently, include tachycardia, hypertension, thrombosis, vasodilation, chest pain, dyspepsia, constipation, dry mouth, hypocalcemia, hyperbilirubinemia, edema, elevated liver enzymes, increased serum creatinine concentration, back pain, asthenia, dizziness, depression, rhinitis, cough, dyspnea, epistaxis, rash, pruritus, injection site reactions, and allergic reactions.
RARE: Rare adverse effects, following long-term busulfan administration, include the development of cataracts, pulmonary fibrosis, cardiac toxicity (cardiac tamponade, myocardial fibrosis), cholestasis, hemorrhagic cystitis, and the development of an Addison-like syndrome. Aplastic anemia has been rarely reported with high oral doses of busulfan as well as with chronic oral busulfan therapy at standard therapeutic doses.

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

ACUTE CLINICAL EFFECTS

SUMMARY

PHARMACOLOGY: Busulfan is a bifunctional alkylating agent whose chemical structure consists of two labile methanesulfonate groups that are attached to opposite ends of a four carbon alkyl chain. Its cytotoxicity is related to the alkylation of DNA due to the production of reactive carbonium ions caused by the release of the methanesulfonate groups when busulfan is hydrolyzed in an aqueous medium.
EPIDEMIOLOGY: Exposure may occur; however, overdose is rare.
OVERDOSE: Busulfan overdose information is limited. Overdose effects are anticipated to be an extension of adverse effects at therapeutic doses. Alopecia, nausea, vomiting, stomatitis, anorexia, and pancytopenia were reported in a 4-year-old child following a single dose ingestion of 140 mg. A total oral busulfan dose of 23.3 mg/kg was inadvertently administered to a 2-year-old child who survived without sequelae; however, an acute busulfan dose of 2.4 grams was fatal in a 10-year-old child.
COMMON ADVERSE EFFECTS: Commonly reported adverse reactions, with an incidence of greater than 60%, include myelosuppression (ie, granulocytopenia, thrombocytopenia, anemia), nausea, vomiting, stomatitis, anorexia, diarrhea, abdominal pain, hypomagnesemia, hypokalemia, hyperglycemia, insomnia, fever, anxiety, and headache. Seizures, coma, and veno-occlusive liver disease have been associated, in children and adults, with high-dose therapeutic administration of busulfan.
INFREQUENT ADVERSE EFFECTS: Adverse effects, reported less frequently, include tachycardia, hypertension, thrombosis, vasodilation, chest pain, dyspepsia, constipation, dry mouth, hypocalcemia, hyperbilirubinemia, edema, elevated liver enzymes, increased serum creatinine concentration, back pain, asthenia, dizziness, depression, rhinitis, cough, dyspnea, epistaxis, rash, pruritus, injection site reactions, and allergic reactions.
RARE ADVERSE EFFECTS: Rare adverse effects, following long-term busulfan administration, include the development of cataracts, pulmonary fibrosis, cardiac toxicity (cardiac tamponade, myocardial fibrosis), cholestasis, hemorrhagic cystitis, and the development of an Addison-like syndrome. Aplastic anemia has been rarely reported with high oral doses of busulfan as well as with chronic oral busulfan therapy at standard therapeutic doses.

Busulfan may be administered at high doses for short periods of time, or administered at low or moderate doses for long periods of time (eg, months or years). Acute adverse effects may result from short-term exposures. Similar effects may also occur following long-term administration.

Subjective symptoms of intoxication are not likely to occur immediately following excessive ingestion of busulfan. Most of the toxic effects are delayed and occur with prolonged drug therapy.

Busulfan is available in tablet form and can be toxic if ingested. A total acute dose of 2.4 g (120 tablets) caused death in a 10-year-old boy (Bishop & Wassom, 1986). Little is known regarding toxicity or lethality in humans by other routes of exposure. Toxicity and lethality, however, have been produced in mice following intraperitoneal administration (PDR, 1996).

Ingestion of high concentrations of busulfan may cause seizures and loss of consciousness. Seizures have been observed most frequently on the 3rd or 4th day of high dose (16 mg/kg to 28 mg/kg total dose) busulfan treatment (Murphy et al, 1992; Vassal et al, 1990). The lowest dose associated with seizures is 8 mg/kg administered intermittently over 2 days (RTECS , 1996).

Decreased production of platelets may also be observed with low dose treatment; increasing drug concentrations suppress red blood cell production. High drug concentrations can result in a general suppression of all types of blood cells (Gilman, 1990). Subsequent effects, such as bleeding, anemia, and infection can occur (PDR, 1996).

Pancytopenia (general suppression of all types of blood cells) is the most serious adverse effect of busulfan therapy and usually results from failure to discontinue administration of busulfan at the first indication of unusual bone marrow suppression (PDR, 1996).

Other adverse reported effects include urticaria (rash with itching), dryness and fragility of the skin, dryness of the mouth, other skin disturbances (erythema multiforme, erythema nodosum, cheilosis), and hair loss. Most of these adverse effects are documented in single case reports and clear evidence of busulfan as the sole causative agent is lacking (PDR, 1996).

Busulfan is frequently used in combination with other drugs, bone marrow transplantation, and irradiation. Adverse effects can occur during or shortly after application of these combined therapies. The most common adverse effects include oral mucositis, hepatic veno-occlusive disease (HVOD), interstitial pneumonia (IP), and hemorrhagic cystitis (Nevill et al, 1991; Parr et al, 1991; Vaughan et al, 1991).

Oral mucositis, HVOD, and IP are potentially fatal effects. Seizures, intracranial hemorrhage, cardiac arrhythmias, congestive heart failure, mild diarrhea, nausea, vomiting, gastrointestinal bleeding, and sepsis have also been reported (Chopra et al, 1991; Nevill et al, 1991; Ratanatharathorn et al, 1992) Vaughn et al, 1991). Graft-versus-host disease is a life threatening complication which affects multiple organ systems, but is more directly related to bone marrow transplantation than to busulfan administration.

Combined therapies may increase the likelihood of adverse effects. Administration of busulfan and cyclophosphamide has increased the risk of hepatic veno-occlusive disease, hemorrhagic cystitis, and skin rashes (Morgan et al, 1991).

Mucositis, skin rash, transient fever, nausea, vomiting, and hepatic veno-occlusive disease have been noted in patients receiving busulfan, cyclophosphamide, and etoposide prior to bone marrow transplantation (Vaughan et al, 1991).

Adverse side effects resulting from combined therapies are not consistently reported in the literature. In many instances, careful drug dosage selection and close patient supervision has resulted in benefits which outweigh the adverse effects of combined therapy (Crilley et al, 1990; Brodsky et al, 1990; von Bueltzingsloewen et al, 1993).

CHRONIC CLINICAL EFFECTS

Busulfan can cause bone marrow suppression. Recovery from busulfan bone marrow effects is possible if the drug is discontinued, but may take 1 month to two years and may require considerable supportive care during severe bone marrow depression (PDR, 1996).

Other adverse effects have been noted with prolonged oral administration of busulfan. Diffuse pulmonary fibrosis is an uncommon, but potentially fatal, consequence of long term therapy (Kobayashi et al, 1990; Pearl, 1977; Vergnon et al, 1988). Busulfan-associated pulmonary fibrosis has an estimated 84% mortality rate (Massin, 1987).

Symptoms of this condition include breathing difficulties, persistent cough, chest congestion, and low grade fever, and generally appear within eight months to ten years after busulfan therapy has been initiated (Kobayashi et al, 1990) Massin, 1987). Busulfan administration must be immediately discontinued in the event of pulmonary fibrosis.

Abnormal cellular changes and fibrosis involving organs other than the lung have also been reported. A case of myocardial fibrosis has been associated with a 9 year course of busulfan treatment (Weinberger et al, 1975). Fibrosis involving the heart has also occurred in a man undergoing a 4-year period of intermittent busulfan treatment (Terpstra & de Maat, 1989). Cellular abnormalities involving the lymph nodes, pancreas, thyroid, adrenal glands, bone marrow, and liver have also occurred (PDR, 1996).

Hepatitis has been suspected to result from an 8-year course of busulfan therapy, as clinical improvement and normal liver enzyme levels were noted after the drug was discontinued (Morris & Guthrie, 1988). Symptoms of hepatitis in this case included fever and abdominal pain. Liver enlargement and jaundice are also indicators of hepatitis.

Esophageal varices, abnormal liver function tests, and abnormal liver biopsies have been reported in patients treated concurrently with busulfan and thioguanine (Key et al, 1987). The onset of esophageal varices has occurred following a treatment period of 6 to 45 months.

A syndrome resembling adrenal insufficiency may develop during the course of busulfan treatment, with symptoms of abrupt onset of weakness, fatigue, weight loss, decreased appetite, nausea, vomiting, and skin discoloration. Symptoms may resolve with discontinuation of busulfan. Persistent effects have also been reported (PDR, 1996).

Hyperuricemia is common in individuals with chronic myelogenous leukemia, and is also a side effect of busulfan treatment and other therapies used in cancer treatment (Gilman, 1990). Hyperuricemia can cause kidney stones and kidney damage (PDR, 1996).

Busulfan has been implicated in the development of hemorrhagic cystitis (Millard, 1981; Pode et al, 1983). Symptoms of hemorrhagic cystitis may include blood in the urine, frequent and painful urination, urinary incontinence, lower abdominal pain, and fever. The condition may spontaneously resolve upon discontinuation of the drug.

Darkening of the skin is a common reaction to busulfan, occurring in approximately 5 to 10% of treated individuals (PDR, 1996).

Other skin effects, such as rashes, itching, dry mouth, cheilosis (red lips, cracked corners of the mouth), and myasthenia gravis have been associated with busulfan therapy. Myasthenia gravis is a progressive disease characterized by significant muscle weakness and fatigue. A clear casual relationship between busulfan exposure and many of these effects is lacking (PDR, 1996).

Cataracts are a rare complication of long-term busulfan administration in humans (Fraunfelder & Meyer, 1983). Oral doses approximately 10 times those used therapeutically have caused irreversible cataracts in rats (Solomon et al, 1955). Lower busulfan doses did not cause cataracts in this animal model.

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

Prehospital gastrointestinal decontamination is generally not recommended because of the potential for CNS depression or persistent seizures and subsequent aspiration.

-RANGE OF TOXICITY

MINIMUM LETHAL EXPOSURE

PEDIATRIC

An acute busulfan dose of 2.4 grams was fatal in a 10-year-old child (Prod Info BUSULFEX(R) intravenous injection, 2015).

MAXIMUM TOLERATED EXPOSURE

ADULT

Seizures with loss of consciousness occurred after receiving 3 to 4 doses of high-dose busulfan therapy, 4 milligrams/kilogram/day. All of the patients recovered following supportive care (Marcus & Goldman, 1984; Vasta et al, 1992).

PEDIATRIC

A 4-year-old child ingested 140 milligrams of busulfan, as a single dose, and developed nausea, vomiting, stomatitis, anorexia, pancytopenia, and alopecia. The patient recovered following supportive care (De Oliveira et al, 1963).
A 2-year-old child inadvertently received a total oral dose of 23.3 milligrams/kilogram and survived without sequelae (Prod Info BUSULFEX(R) intravenous injection, 2015).

Carcinogenicity Ratings for CAS55-98-1 :

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): 1 ; Listed as: 1,4-Butanediol dimethanesulfonate (Busulphan; Myleran)

1 : The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.

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 CAS55-98-1 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

BUSULFAN
- LD50- (INTRAPERITONEAL)MOUSE:
- LD50- (ORAL)MOUSE:
- LD50- (SUBCUTANEOUS)MOUSE:
- LD50- (INTRAPERITONEAL)RAT:
- LD50- (INTRAVENOUS)RAT:
- LD50- (SUBCUTANEOUS)RAT:

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS55-98-1 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS55-98-1 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS55-98-1 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS55-98-1 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS55-98-1 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS55-98-1 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS55-98-1 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS55-98-1 (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 CAS55-98-1 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS55-98-1 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS55-98-1 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS55-98-1 (EPA, 2005):

Not Listed

LABELS

NFPA

NFPA Hazard Ratings for CAS55-98-1 (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 55-98-1.

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 CAS55-98-1 (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 CAS55-98-1 (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 CAS55-98-1 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS55-98-1 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS55-98-1 (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 CAS55-98-1 (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

BUSULFAN - 246.3 (S Sweetman , 2000)

TREOSULFAN - 278.3 (S Sweetman , 2000)

DESCRIPTION/PHYSICAL STATE

BUSULFAN - A white or almost white crystalline powder that is slightly soluble in water, alcohol, and ether, and is freely soluble in acetone and in chloroform (S Sweetman , 2000).

-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.

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Basch E, Prestrud AA, Hesketh PJ, et al: Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2011; 29(31):4189-4198.

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BUSULFAN AND RELATED AGENTS

Classification | Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents