CHLORAMBUCIL

Chlorambucil is used to treat patients with chronic lymphatic (lymphocytic) leukemia, malignant lymphomas, including lymphosarcoma, giant follicular lymphoma, and Hodgkin's disease (Prod Info LEUKERAN(R) oral tablets, 2011).

FORMS

Chlorambucil is available as 2 mg oral tablets (Prod Info LEUKERAN(R) oral tablets, 2011).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Chlorambucil is used to treat patients with chronic lymphatic (lymphocytic) leukemia, malignant lymphomas, including lymphosarcoma, giant follicular lymphoma, and Hodgkin's disease.

PHARMACOLOGY: Chlorambucil is an aromatic nitrogen mustard derivative and alkylating agent that interferes with DNA replication and induces cellular apoptosis by accumulation of cytosolic p53 and activation of the apoptosis promoter, BAX.

TOXICOLOGY: After an overdose, the effects of decreased DNA synthesis and cell death are noticed primarily in organ systems with rapidly dividing cells (bone marrow, gastrointestinal tract).

EPIDEMIOLOGY: Overdose is rare, but can be life-threatening.

WITH POISONING/EXPOSURE

Excessive dosage or prolonged administration can induce severe myelosuppression. Patients who receive a total of 6.5 mg/kg or more in one course of therapy with continuous dosing are most likely to develop severe neutropenia. Nausea, vomiting, acute renal failure, agitation, irritability, ataxia, muscle twitching, seizures, lethargy, myoclonus, and coma have also been reported.

WITH THERAPEUTIC USE

Myelosuppression is the dose-limiting toxicity of chlorambucil and has an onset of 1 to 14 days. Leukopenia, thrombocytopenia, neutropenia, anemia, and pancytopenia have been reported. Blood counts continue to fall after discontinuing therapy; a nadir is usually reached in 10 days to 2 weeks. Bone marrow effects are most often reversible; however, irreversible bone marrow failure has been reported. INFREQUENT: Nausea, vomiting, diarrhea, and oral ulceration. RARE: Tremors, muscular twitching, myoclonus, confusion, agitation, ataxia, flaccid paresis, hallucinations, seizures, skin hypersensitivity reactions (eg, rashes, urticaria, angioedema, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), pulmonary fibrosis, hepatotoxicity, jaundice, drug fever, peripheral neuropathy, and interstitial pneumonia.

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

ACUTE CLINICAL EFFECTS

SUMMARY

PHARMACOLOGY: Chlorambucil is an aromatic nitrogen mustard derivative and alkylating agent that interferes with DNA replication and induces cellular apoptosis by accumulation of cytosolic p53 and activation of the apoptosis promoter, BAX.
TOXICOLOGY: After an overdose, the effects of decreased DNA synthesis and cell death are noticed primarily in organ systems with rapidly dividing cells (bone marrow, gastrointestinal tract).
EPIDEMIOLOGY: Overdose is rare, but can be life-threatening.
ADVERSE EFFECTS: Myelosuppression is the dose-limiting toxicity of chlorambucil and has an onset of 1 to 14 days. Leukopenia, thrombocytopenia, neutropenia, anemia, and pancytopenia have been reported. Blood counts continue to fall after discontinuing therapy; a nadir is usually reached in 10 days to 2 weeks. Bone marrow effects are most often reversible; however, irreversible bone marrow failure has been reported. INFREQUENT: Nausea, vomiting, diarrhea, and oral ulceration. RARE: Tremors, muscular twitching, myoclonus, confusion, agitation, ataxia, flaccid paresis, hallucinations, seizures, skin hypersensitivity reactions (eg, rashes, urticaria, angioedema, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), pulmonary fibrosis, hepatotoxicity, jaundice, drug fever, peripheral neuropathy, and interstitial pneumonia.
OVERDOSE: Overdose data are limited; effects are likely an extension of adverse events. Excessive dosage or prolonged administration can induce severe myelosuppression. Patients who receive a total of 6.5 mg/kg or more in one course of therapy with continuous dosing are most likely to develop severe neutropenia. Nausea, vomiting, acute renal failure, agitation, irritability, ataxia, muscle twitching, seizures, lethargy, myoclonus, and coma have also been reported.

DERMATOLOGIC

SKIN HYPERSENSITIVITY REACTIONS including rare reports of skin rash progressing to erythema multiforme, and Stevens-Johnson syndrome have been reported. Allergic reactions such as urticaria and angioedema have also been reported following initial or subsequent dosing (Prod Info LEUKERAN(R) oral tablets, 2011).

GASTROINTESTINAL

NAUSEA AND VOMITING: Although reported infrequently, nausea and vomiting have occurred following chlorambucil administration (Prod Info LEUKERAN(R) oral tablets, 2011). Single oral doses of 20 milligrams or more may also cause nausea and vomiting (Prod Info LEUKERAN(R) oral tablets, 2011).

GENITOURINARY

ACUTE RENAL FAILURE: CASE REPORT: Acute renal failure NOT associated with rhabdomyolysis was reported in a 38-year-old man who ingested 250 mg in a single dose (Blank et al, 1983).

HEENT

BLINDNESS: Transient blindness was reported in one child who had received 1.5 mg/kg per day (32 mg total). This has not been a common finding (Ammenti et al, 1980). Another case involving blindness with optic atrophy has been reported (Yiannakis & Larner, 1993).

HEMATOLOGIC

MYELOSUPPRESSION: Myelosuppression is the dose-limiting toxicity of chlorambucil and has an onset of 1 to 14 days. Leukopenia, thrombocytopenia, neutropenia, and anemia have been reported (Ezlindi & Stutzman, 1965; Galton, 1961; Masturon, 1960). Blood counts continue to fall after discontinuing therapy; a nadir is usually reached in 10 days to 2 weeks (Prod Info LEUKERAN(R) oral tablets, 2011; Knoben & Anderson, 1988b).

Bone marrow effects are most often reversible; however, irreversible bone marrow failure has been reported. Excessive dosage or prolonged administration can induce severe bone marrow depression (Prod Info LEUKERAN(R) oral tablets, 2011; Krakoff, 1971). Patients who receive a total of 6.5 mg/kg or more in one course of therapy with continuous dosing are most likely to develop severe neutropenia (Prod Info LEUKERAN(R) oral tablets, 2011).
Excessive dosage or prolonged administration can induce severe bone marrow depression (Prod Info LEUKERAN(R) oral tablets, 2011; Krakoff, 1971). As the total dose approaches 6.5 milligrams/kilogram, there is a risk of causing irreversible bone marrow damage (Prod Info LEUKERAN(R) oral tablets, 2011).

HEPATIC

HEPATOTOXICITY: Hepatotoxicity and jaundice have been reported following chlorambucil administration (Prod Info LEUKERAN(R) oral tablets, 2011; Braunwald et al, 1990).

NEUROLOGIC

Some tremors, muscular twitching, myoclonia, confusion, ataxia, and flaccid paresis have occurred following chlorambucil administration; however, resolution occurs following discontinuation of the drug. Peripheral neuropathy and, rarely, seizures have also been reported (Prod Info LEUKERAN(R) oral tablets, 2011).
SEIZURES: Seizures have been reported in both adults and children (Wolfson & Olney, 1957; Byrne et al, 1981; Blank et al, 1983; Salloum et al, 1997).

Onset is within 1.5 to 5 hours after chlorambucil overdose via ingestion. This is a rare side effect during therapeutic or slightly higher doses. Onset of seizures have been reported up to 90 days after initiation of therapy (LaDelfa et al, 1985; Williams et al, 1978; Naysmith & Robson, 1979; Salloum et al, 1997).

RESPIRATORY

Chlorambucil administration has been associated with the occurrence of acute pneumonitis, interstitial pneumonia, and pulmonary infiltrates. In addition, one case of noncardiogenic pulmonary edema has been reported (Prod Info LEUKERAN(R) oral tablets, 2011; Crestani et al, 1994; Braunwald et al, 1990; Cannon, 1990).

OTHER

DRUG FEVER: Drug fever has been associated with chlorambucil therapy presenting as fever, rigors, and malaise within hours to days of chlorambucil therapy initiation, often following a drug-free interval. Other symptoms include skin rash, lymphadenopathy, vomiting, diarrhea and hypotension, which resolve upon discontinuation of chlorambucil and reoccurs within the same time period when chlorambucil is reinitiated (Weber et al, 2007).

CHRONIC CLINICAL EFFECTS

WITH POISONING/EXPOSURE

Seizures occur rarely with therapeutic doses; onset may be up to 90 days after initiation of therapy (LaDelfa et al, 1985; Williams et al, 1978; Naysmith & Robson, 1979). Transient blindness was reported in one child who received 1.5 mg/kg/day (total dose of 32 mg), but this has not been a common finding (Ammenti et al, 1980). Another case involving blindness with optic atrophy has been reported (Yiannakis & Larner, 1993).

WITH THERAPEUTIC USE

Most of the clinical literature on chlorambucil involves repeated or chronic dosing. The usual therapeutic dose is 0.1 to 0.2 mg/kg/day for a period of 3 to 6 weeks (Prod Info, 1984). Maintenance therapy may involve doses as low as 0.03 mg/kg/day (Prod Info Leukeran(R), 1993). Some patients take the drug for several years (Dumont et al, 1980).
Many patients develop a slowly progressive lymphopenia during treatment (Prod Info, 1984). Severe neutropenia and irreversible bone marrow damage can be caused by a total dose greater than 6.5 mg/kg (Rudd et al, 1975) Prod Info, 1984); counts may continue to fall after discontinuation of therapy with the nadir in approximately 2 weeks. Most depressions are reversible (Prod Info Leukeran(R), chlorambucil, 1990; Knoben & Anderson, 1988).
Repeated exposure to chlorambucil has been neurotoxic. Doses of 2 to 4 mg/kg/day in immunosuppression therapy have been associated with reversible central nervous system toxicity in adults (Ciobanu et al, 1987). Children appear to be especially susceptible to chlorambucil-induced central nervous toxicity (Ichida et al, 1985).
Therapeutic chlorambucil treatment can have dermatologic effects. Erythematous urticarial-like plaques developed over the nose and cheeks of a 61-year-old woman after 8 days of treatment at 4 mg/day (Peterman & Braunstein, 1986). Exfoliative dermatitis has occurred in 3 patients (Hitchins et al, 1987).
Toxic epidermal necrolysis, with confluent maculopapular erythema and flaccid blisters has been reported in several patients shortly after initiation of chlorambucil therapy (Barone et al, 1990; Pietrantonio et al, 1990). One case of allergic erythema multiforme had a fatal outcome (Hitchins et al, 1987). Allergic skin rashes have been reported (Prod Info Leukeran(R), chlorambucil, 1990).
As with acute exposure, gastrointestinal effects in chronic exposure can include nausea, vomiting, diarrhea, and oral cavity ulcerations (JEF Reynolds , 1996).
Other reported effects of chronic exposure include acute pneumonitis, pulmonary fibrosis, pulmonary infiltrates, cystitis, jaundice, immune-mediated hemolytic anemia, myelofibrosis, and glomerulonephritis in children (JEF Reynolds , 1996; Crestani et al, 1994a; Prod Info Leukeran(R), chlorambucil, 1990; Braunwald et al, 1990a; Giles et al, 1990; Cannon, 1990a; Carr, 1986).
Chlorambucil induced myoclonus in two elderly adults receiving low doses for treatment of lymphoma. This is the first report of myoclonus at low doses in persons with no previous history (Wyllie et al, 1997).

-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

MAXIMUM TOLERATED EXPOSURE

NEUROTOXICITY

High dose chlorambucil (2 to 4 mg/kg/day) in autologous bone marrow transplantation for ovarian carcinoma was associated with the development of reversible central nervous system toxicity in 3 adults (Ciobanu et al, 1987).

SEIZURES

In children, chlorambucil dosages which have caused seizures are reported to range from 0.125 to 6.8 mg/kg.
In adults, these doses range from 5 to 250 mg/day (Alberts et al, 1979; McLean et al, 1979; Shotton & Monie, 1963; Knisley et al, 1971; Salloum et al, 1997).
In one case report, 250 mg of chlorambucil taken in a single dose caused seizures and acute renal failure. No permanent sequelae were noted (Blank et al, 1983).

NEUTROPENIA

Neutropenia is usually present in patients receiving in excess of 6.5 mg/kg in a total dose (Prod Info LEUKERAN(R) oral tablets, 2011).
PEDIATRIC DOSING: Chlorambucil was used to induce remission within 6 months in 41 (52%) pediatric patients with juvenile chronic arthritis. Chlorambucil was initiated stepwise to a maximum dose of 0.2 mg/kg/day. Long-term remission (median follow-up 8.5 years) was attained in 14 (18%) patients. Chlorambucil was withdrawn in 16 patients due to side effects of either rash or bone marrow depression. Two patients developed leukemia and 17 (22%) experienced 1 to 3 occurrences of herpes zoster infection. At long-term follow-up (8.5 years), 14 (18%) patients were in complete remission without drugs (Savolainen, 1999).

IRREVERSIBLE BONE MARROW DAMAGE

May be seen at doses of greater than 6.5 milligrams/kilogram total dose given therapeutically (Prod Info LEUKERAN(R) oral tablets, 2011).

PANCYTOPENIA

In a case report, 280 mg (4.1 mg/kg) was accidentally ingested over a 5-day period in an adult. Only mild pancytopenia was seen (Enck & Bennett, 1977).

Carcinogenicity Ratings for CAS305-03-3 :

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: Chlorambucil

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 ): K ; Listed as: Chlorambucil

K : KNOWN = Known to be a human carcinogen

TOXICITY AND RISK ASSESSMENT VALUES

EPA IRIS

EPA Risk Assessment Values for CAS305-03-3 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

LD50- (INTRAPERITONEAL)MOUSE:
- 30 mg/kg (RTECS , 1999)
LD50- (ORAL)MOUSE:
- 101 mg/kg (RTECS , 1999)
LD50- (SUBCUTANEOUS)MOUSE:
- 115 mg/kg (RTECS , 1999)
LD50- (INTRAPERITONEAL)RAT:
- 14 mg/kg (RTECS , 1999)
LD50- (ORAL)RAT:
- 76 mg/kg (RTECS , 1999)
LDLo- (INTRAVENOUS)DOG:
- 3 mg/kg (RTECS , 1999)
LDLo- (INTRAVENOUS)PRIMATE:
- 3 mg/kg (RTECS , 1999)
LDLo- (SUBCUTANEOUS)RAT:
- 32 mg/kg (RTECS , 1999)
TDLo- (ORAL)HUMAN:
- 13 mg/kg -- menstrual cycle changes (RTECS , 1999)
- 82,600 mcg/kg -- interstitial fibrosis (RTECS , 1999)

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS305-03-3 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS305-03-3 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS305-03-3 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS305-03-3 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS305-03-3 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS305-03-3 (U.S. Environmental Protection Agency, 2010):

Listed as: Benzenebutanoic acid, 4-[bis(2-chloroethyl)amino]-
Final Reportable Quantity, in pounds (kilograms):

10 (4.54)

Additional Information:
Listed as: Chlorambucil
Final Reportable Quantity, in pounds (kilograms):

10 (4.54)

Additional Information:

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS305-03-3 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS305-03-3 (U.S. Environmental Protection Agency, 2010b):

Listed as: Benzenebutanoic acid, 4-[bis(2-chloroethyl)amino]-
P or U series number: U035
Footnote:
Listed as: Chlorambucil
P or U series number: U035
Footnote:
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 CAS305-03-3 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS305-03-3 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS305-03-3 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS305-03-3 (EPA, 2005):

Not Listed

LABELS

NFPA

NFPA Hazard Ratings for CAS305-03-3 (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 305-03-3.

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 CAS305-03-3 (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 CAS305-03-3 (NFPA, 2002):

Not Listed

REACTIVITY HAZARD

Hydrolyzes in water (Prod Info, 1984).

EVACUATION PROCEDURES

SUMMARY

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

AIHA ERPG Values for CAS305-03-3 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS305-03-3 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS305-03-3 (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 CAS305-03-3 (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

304.23

DESCRIPTION/PHYSICAL STATE

This compound exists as flattened needles from petroleum ether (Budavari, 1989).

FREEZING/MELTING POINT

MELTING POINT

64-66 degrees C (Budavari, 1989)

SOLUBILITY

IN ORGANIC SOLVENTS

ACETONE: soluble in 2 parts (Budavari, 1989)
ALCOHOL: soluble in 1.5 parts (at 20 degrees C) (Budavari, 1989)
CHLOROFORM: soluble in 2.5 parts (Budavari, 1989)
ETHER: soluble (Budavari, 1989)

OTHER/PHYSICAL

DISSOCIATION CONSTANT

pKa = 5.8 (Dorr & Fritz, 1980)

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

Alberts DS, Chang SY, & Chen HS: Pharmacokinetics and metabolism of chlorambucil in man: a preliminary report. Cancer Treat Rev 1979; 6:9.

American Conference of Governmental Industrial Hygienists : ACGIH 2010 Threshold Limit Values (TLVs(R)) for Chemical Substances and Physical Agents and Biological Exposure Indices (BEIs(R)), American Conference of Governmental Industrial Hygienists, Cincinnati, OH, 2010.

Ammenti A, Reitter B, & Muller-Wiefel DE: Chlorambucil neurotoxicity: report of two cases. Helv Paediatr Acta 1980; 35:281-287.

Ando S, Tanaka O, & Tatewaki R: Comparative study on the pathogenesis of drug-induced and spontaneously developed neural tube defects (NTDs) in mouse embryos. Senten Ijo 1990; 30:271.

Ashby J & Tinwell H: Clastogenicity of chlorambucil to the mouse bone marrow: consideration in relation to its genetic specificity of action in some assays. Mutagenesis 1993; 8:373-375.

Aymard JP, Frustin J, & Witz F: Acute leukaemia after prolonged chlorambucil treatment for non-malignant disease: report of a new case and literature survey. Acta Haematol 1980; 63:283-285.

Aymard JP, Lederlin P, & Witz F: Acute leukaemia following prolonged chlorambucil treatment for non-neoplastic disease - a study of two cases and literature review. Acta Clin Belg 1983; 38:228-235.

Barone C, Cassano A, & Astone A: Toxic epidermal necrolysis during chlorambucil therapy in chronic lymphocytic leukaemia. Eur J Cancer 1990; 26:1262.

Bean CL & Galloway SM: Evaluation of the need for a late harvest time in the assay for chromosome aberrations in Chinese hamster ovary cells. Mutat Res 1993; 292:3-16.

Berger MR, Habs M, & Schmahl D: Long-term toxicology effects of prednimustine in comparison with chlorambucil, prednisolone, and chlorambucil plus prednisolone in Sprague-Dawley rats. Semin Oncol 1986; 13(Suppl 1):8-13.

Berk PD, Goldberg JD, & Silverstein MN: Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med 1981; 304:441-447.

Bermas BL & Hill JA: Effects of immunosuppressive drugs during pregnancy. Arthritis Rheum 1995; 38:1722-1732.

Blanc AP, Gastaut JA, & Sebahoun G: Acute leukaemia during immunosuppressive treatment. One case. Nouv Presse Med 1981; 10:1717-1719.

Blank DW, Nanji AA, & Schreiber DH: Acute renal failure and seizures associated with chlorambucil overdose. J Toxicol Clin Toxicol 1983; 20:361-365.

Boivin JF, Hutchison GB, & Zauber AG: Incidence of second cancers in patients treated for Hodgkins disease. J Nat Cancer Inst 1995; 87:732-741.

Braunwald E, Isselbacher KJ, & Petersdorf RG: Harrison's Principles of Internal Medicine, 12th ed, McGraw-Hill Book Company, New York, NY, 1990a.

Braunwald E, Isselbacher KJ, Petersdorf RG, et al (Eds): Harrison's Principles of Internal Medicine, 12th. McGraw-Hill Book Company, New York, NY, 1990.

Briggs GG, Freeman RK, & Yaffe SJ: Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 4th ed, Williams & Wilkins, Baltimore, MD, 1994.

Brophy GM, Bell R, Claassen J, et al: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17(1):3-23.

Brummett ES & Johnson EM: Morphological alterations in the developing fetal rat limb due to maternal injection of chlorambucil. Teratology 1979; 20:279-287.

Buriot D, Prieur AM, & Lebranchu Y: Acute leukemia in 3 children with chronic juvenile arthritis treated with chlorambucil. Arch Fr Pediatr 1979; 36:592-598.

Byrne TN Jr, Moseley TA III, & Finer MA: Myoclonic seizures following chlorambucil overdose. Ann Neurol 1981; 9:191-194.

Cameron S: Chlorambucil and leukemia. N Engl J Med 1977; 296:1065.

Cannon GW: Pulmonary complications of antirheumatic drug therapy. Semin Arthritis Rheum 1990; 19:353-364.

Cannon GW: Pulmonary complications of antirheumatic drug therapy. Semin Arthritis Rheum 1990a; 19:353-364.

Carr ME Jr: Chlorambucil induced pulmonary fibrosis: report of a case and review. VA Med 1986; 113:677-680.

Cavaliere A, Pietropaoli N, & Alberti PF: Chlorambucil carcinogenesis in BALB/c mice. Cancer Lett 1990; 55:115-120.

Chamberlain JM, Altieri MA, & Futterman C: A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Ped Emerg Care 1997; 13:92-94.

Chang SY: Modification of HPLC analysis of melphalan in plasma. J Pharm Sci 1978; 67:679-681.

Chin RF , Neville BG , Peckham C , et al: Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol 2008; 7(8):696-703.

Choonara IA & Rane A: Therapeutic drug monitoring of anticonvulsants state of the art. Clin Pharmacokinet 1990; 18:318-328.

Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.

Ciobanu N, Runowicz C, & Gucalp R: Reversible central nervous system toxicity associated with high-dose chlorambucil in autologous bone marrow transplantation for ovarian carcinoma. Cancer Treat Rep 1987; 71:1324-1325.

Clark ST, Radford JA, & Crowther D: Gonadal function following chemotherapy for Hodgkins disease - a comparative study of MVPP and a seven-drug hybrid regimen. J Clin Oncol 1995; 13:134-139.

Crestani B, Jaccard A, & Israel-Biet D: Chlorambucil-associated pneumonitis. Chest 1994a; 105:634-636.

Crestani B, Jaccard A, Israel-Biet D, et al: Chlorambucil-associated pneumonitis. Chest 1994; 105:634-636.

DFG: List of MAK and BAT Values 2002, Report No. 38, Deutsche Forschungsgemeinschaft, Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Wiley-VCH, Weinheim, Federal Republic of Germany, 2002.

Dorr RT & Fritz WL: Cancer Chemotherapy Handbook, Elsevier, New York, NY, 1980.

Dumont J, Thiery JP, & Mazabraud A: Acute myeloid leukemia following non-Hodgkin's lymphoma: danger of prolonged use of chlorambucil as maintenance therapy. Nouv Rev Fr Hematol 1980; 22:391-404.

Dupuis LL & Nathan PC: Options for the prevention and management of acute chemotherapy-induced nausea and vomiting in children. Paediatr Drugs 2003; 5(9):597-613.

EPA: Search results for Toxic Substances Control Act (TSCA) Inventory Chemicals. US Environmental Protection Agency, Substance Registry System, U.S. EPA's Office of Pollution Prevention and Toxics. Washington, DC. 2005. Available from URL: http://www.epa.gov/srs/.

Ehrsson H, Lonroth U, & Wallin I: Degradation of chlorambucil in aqueous solution - influence of human albumin binding. J Pharm Pharmacol 1981; 33:313.

Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.

Elzouki AY, al Nassar K, & al Ali M: Sister chromatid exchange analysis in monitoring chlorambucil therapy in primary nephrotic syndrome of childhood. Pediatr Nephrol 1991; 5:59-61.

Enck RE & Bennett JM: Inadvertent chlorambucil overdose in adults. State J Med 1977; 77:1480-1481.

Ezlindi EZ & Stutzman L: Chlorambucil therapy for lymphomas and chronic lymphocytic leukemia. JAMA 1965; 191:444.

FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.

Ferguson LR, Palmer BD, & Denny WA: Microbial mutagenicity of chlorambucil, its half-mustard and mitomycin C: a modified screening strategy for genetic toxicology of bis-alkylating anti-tumour drugs. Anticancer Drug Des 1988; 3:67-76.

Flaherty L, Messer A, & Russell LB: Chlorambucil-induced mutations in mice recovered in homozygotes. Proc Natl Acad Sci USA 1992; 89:2859-2863.

Freifeld AG, Bow EJ, Sepkowitz KA, et al: Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 2011; 52(4):e56-e93.

Galton DAG: The use of chlorambucil and steroids in treatment of chronic lymphocytic leukemia. Br J Haematol 1961; 7:73.

Generoso WM, Witt KL, & Cain KT: Dominant lethal and heritable translocation tests with chlorambucil and melphalan in male mice. Mutat Res 1995; 345:167-180.

Giles FJ, Smith MP, & Goldstone AH: Chlorambucil lung toxicity. Acta Haematol 1990; 83:156-158.

Goldhirsch A, Pirovino M, & Coninx S: Acute erythroleukemia following chemotherapy for Hodgkin's disease. Am J Med Sci 1980; 280:53-56.

Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.

Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.

Grant WM: Toxicology of the Eye, 3rd ed, Charles C Thomas, Springfield, IL, 1986, pp 252.

Green AA & Naiman JL: Chlorambucil poisoning. Am J Dis Child 1968; 116:190-191.

HSDB : Hazardous Substances Data Bank. National Library of Medicine. Bethesda, MD (Internet Version). Edition expires 1996; provided by Truven Health Analytics Inc., Greenwood Village, CO.

Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.

Hartman LC, Tschetter LK, Habermann TM, et al: Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia.. N Engl J Med 1997; 336:1776-1780.

Hegenbarth MA & American Academy of Pediatrics Committee on Drugs: Preparing for pediatric emergencies: drugs to consider. Pediatrics 2008; 121(2):433-443.

Hitchins RN, Hocker GA, & Thomson DB: Chlorambucil allergy - a series of three cases. Aust NZ J Med 1987; 17:600-602.

Hoorn AJ, Custer LL, & Myhr BC: Detection of chemical mutagens using Muta Mouse: a transgenic mouse model. Mutagenesis 1993; 8:7-10.

Hvidberg EF & Dam M: Clinical pharmacokinetics of anticonvulsants. Clin Pharmacokinet 1976; 1:161.

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide), 97, International Agency for Research on Cancer, Lyon, France, 2008.

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol, 88, International Agency for Research on Cancer, Lyon, France, 2006.

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Household Use of Solid Fuels and High-temperature Frying, 95, International Agency for Research on Cancer, Lyon, France, 2010a.

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines, 89, International Agency for Research on Cancer, Lyon, France, 2007.

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans : IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Some Non-heterocyclic Polycyclic Aromatic Hydrocarbons and Some Related Exposures, 92, International Agency for Research on Cancer, Lyon, France, 2010.

IARC: List of all agents, mixtures and exposures evaluated to date - IARC Monographs: Overall Evaluations of Carcinogenicity to Humans, Volumes 1-88, 1972-PRESENT. World Health Organization, International Agency for Research on Cancer. Lyon, FranceAvailable from URL: http://monographs.iarc.fr/monoeval/crthall.html. As accessed Oct 07, 2004.

IARC: Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man, 9, International Agency for Research on Cancer, World Health Organization, Geneva, Switzerland, 1975, pp 127-131.

Ichida F, Konishi T, & Asada R: Chlorambucil central nervous toxicity: a significant side effect of chlorambucil therapy in childhood nephrotic syndrome. Eur J Pediatr 1985; 144:283-286.

International Agency for Research on Cancer (IARC): IARC monographs on the evaluation of carcinogenic risks to humans: list of classifications, volumes 1-116. International Agency for Research on Cancer (IARC). Lyon, France. 2016. Available from URL: http://monographs.iarc.fr/ENG/Classification/latest_classif.php. As accessed 2016-08-24.

International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. World Health Organization. Geneva, Switzerland. 2015. Available from URL: http://monographs.iarc.fr/ENG/Classification/. As accessed 2015-08-06.

JEF Reynolds : Martindale: The Extra Pharmacopoeia. The Pharmaceutical Press. London, England (Internet Version). Edition expires 1996; provided by Truven Health Analytics Inc., Greenwood Village, CO.

Kaldor JM, Day NE, & Pettersson F: Leukemia following chemotherapy for ovarian cancer [see comments]. N Engl J Med 1990; 322:1-6.

Kauppi MJ, Savolainen HA, & Anttila VJ: Increased risk of leukaemia in patients with juvenile chronic arthritis treated with chlorambucil. Acta Paediatr 1996; 85:248-250.

Kavlock RJ, Rehnberg BF, & Rogers EH: Chlorambucil induced congenital renal hypoplasia: Effects on basal renal function in the developing rat. Toxicology 1986; 40:247-258.

Kavlock RJ, Rehnberg BF, & Rogers EH: Critical prenatal periods for chlorambucil-induced functional alterations of the rat kidney. Toxicology 1987; 43:51-64.

Knisley RE, Settipane GA, & Albala MM: Unusual reaction to chlorambucil in a patient with chronic lymphocytic leukemia. Arch Dermatol 1971; 104:77.

Knoben JE & Anderson PO (Eds): Handbook of Clinical Drug Data, 6th. Drug Intelligence Publications, Inc, Hamilton, IL, 1988b.

Knoben JE & Anderson PO: Handbook of Clinical Drug Data, 6th ed, Drug Intelligence Publications, Inc, Hamilton, IL, 1988.

Knoben JE & Anderson POKnoben JE & Anderson PO (Eds): Handbook of Clinical Drug Data, 6th. Drug Intelligence Publications, Inc, Hamilton, IL, 1988a.

Krakoff IH: Growth-inhibiting drugs: their anticancer, anti-immune, and teratogenic effects. Drill's Pharmacology in Medicine, 1971, 1971.

Kris MG, Hesketh PJ, Somerfield MR, et al: American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 2006; 24(18):2932-2947.

LaDelfa I, Bayer N, & Myers R: Chlorambucil-induced myoclonic seizures in an adult. J Clin Oncology 1985; 3:1691-1692.

Lawler SD & Lele KP: Chromosomal damage induced by chlorambucil in chronic lymphocytic leukemia. Scand J Hematol 1972; 9:603.

Lerner HJ: Acute myelogenous leukemia in patients receiving chlorambucil as long-term adjuvant chemotherapy for stage II breast cancer. Cancer Treat Rep 1978; 62:1135-1138.

Littlefield LG, Colyer SP, & Sayer AM: Sister-chromatid exchanges in human lymphocytes exposed during Go to four classes of DNA-damaging chemicals. Mutat Res 1979; 67:259-269.

Loddenkemper T & Goodkin HP: Treatment of Pediatric Status Epilepticus. Curr Treat Options Neurol 2011; Epub:Epub.

Manno EM: New management strategies in the treatment of status epilepticus. Mayo Clin Proc 2003; 78(4):508-518.

Masturon JG: Clinical study of the use of chlorambucil in treatment of carcinoma of ovary. Am J Obstet Gynecol 1960; 79:1002.

McLean A, Woods RL, & Catovsky D: Pharmacokinetics and metabolism of chlorambucil in patients with malignant disease. Cancer Treat Rev 1979; 6:33.

Menkes CJ, Levy JP, & Weill B: Acute leukemia with megakaryoblasts. Incidence following immunosuppressive treatment of rheumatoid polyarthritis (French). Nouv Presse Med 1975; 4:2869-2871.

Mortelmans K, Haworth S, & Lawlor T: Salmonella mutagenicity tests. 2. Results from the testing of 270 chemicals. Environ Mutagen 1986; 8(Suppl 7):1-119.

Mueller W & Brandis M: Acute leukemia after cytotoxic treatment for nonmalignant disease in childhood. A case report and review of the literature. Eur J Pediatr 1981; 136:105-108.

NFPA: Fire Protection Guide to Hazardous Materials, 13th ed., National Fire Protection Association, Quincy, MA, 2002.

NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 1, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2001.

NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 2, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2002.

NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 3, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2003.

NRC: Acute Exposure Guideline Levels for Selected Airborne Chemicals - Volume 4, Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council. National Academy Press, Washington, DC, 2004.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,3-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2,4-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Butylene Oxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648083cdbb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,2-Dibromoethane (Proposed). United States Environmental Protection Agency. Washington, DC. 2007g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802796db&disposition=attachment&contentType=pdf. As accessed 2010-08-18.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 1,3,5-Trimethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d68a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for 2-Ethylhexyl Chloroformate (Proposed). United States Environmental Protection Agency. Washington, DC. 2007b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037904e&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Acrylonitrile (Proposed). United States Environmental Protection Agency. Washington, DC. 2007c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648028e6a3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Adamsite (Proposed). United States Environmental Protection Agency. Washington, DC. 2007h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Agent BZ (3-quinuclidinyl benzilate) (Proposed). United States Environmental Protection Agency. Washington, DC. 2007f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ad507&disposition=attachment&contentType=pdf. As accessed 2010-08-18.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Allyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039d9ee&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Arsenic Trioxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480220305&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Automotive Gasoline Unleaded (Proposed). United States Environmental Protection Agency. Washington, DC. 2009a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cc17&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Biphenyl (Proposed). United States Environmental Protection Agency. Washington, DC. 2005j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1b7&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bis-Chloromethyl Ether (BCME) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648022db11&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Boron Tribromide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae1d3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromine Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2007d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648039732a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Bromoacetone (Proposed). United States Environmental Protection Agency. Washington, DC. 2008e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187bf&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Calcium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803ae328&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Carbonyl Sulfide (Proposed). United States Environmental Protection Agency. Washington, DC. 2007e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648037ff26&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Chlorobenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064803a52bb&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Cyanogen (Proposed). United States Environmental Protection Agency. Washington, DC. 2008f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809187fe&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Dimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbf3&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Diphenylchloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091884e&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyl Phosphorodichloridate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480920347&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethylbenzene (Proposed). United States Environmental Protection Agency. Washington, DC. 2008g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809203e7&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ethyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

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.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Hexafluoropropylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064801ea1f5&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Ketene (Proposed). United States Environmental Protection Agency. Washington, DC. 2007. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ee7c&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Aluminum Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Magnesium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Malathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2009k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064809639df&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Mercury Vapor (Proposed). United States Environmental Protection Agency. Washington, DC. 2009b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a087&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Isothiocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a03&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963a57&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyl tertiary-butyl ether (Proposed). United States Environmental Protection Agency. Washington, DC. 2007a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064802a4985&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methylchlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5f4&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Methyldichlorosilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2005a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c646&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN1 CAS Reg. No. 538-07-8) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006a. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN2 CAS Reg. No. 51-75-2) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006b. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Mustard (HN3 CAS Reg. No. 555-77-1) (Proposed). United States Environmental Protection Agency. Washington, DC. 2006c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6cb&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Tetroxide (Proposed). United States Environmental Protection Agency. Washington, DC. 2008n. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648091855b&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Nitrogen Trifluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009l. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e0c&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Parathion (Proposed). United States Environmental Protection Agency. Washington, DC. 2008o. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480963e32&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perchloryl Fluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e268&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Perfluoroisobutylene (Proposed). United States Environmental Protection Agency. Washington, DC. 2009d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26a&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008p. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dd58&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2006d. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020cc0c&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phenyldichloroarsine (Proposed). United States Environmental Protection Agency. Washington, DC. 2007k. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020fd29&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phorate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008q. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096dcc8&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene (Draft-Revised). United States Environmental Protection Agency. Washington, DC. 2009e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a8a08a&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Phosgene Oxime (Proposed). United States Environmental Protection Agency. Washington, DC. 2009f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e26d&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Potassium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005c. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Propargyl Alcohol (Proposed). United States Environmental Protection Agency. Washington, DC. 2006e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec91&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Selenium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec55&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Silane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006g. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d523&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Cyanide (Proposed). United States Environmental Protection Agency. Washington, DC. 2009h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7cbb9&disposition=attachment&contentType=pdf. As accessed 2010-08-15.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sodium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Strontium Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005f. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Sulfuryl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2006h. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020ec7a&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tear Gas (Proposed). United States Environmental Protection Agency. Washington, DC. 2008s. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e551&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tellurium Hexafluoride (Proposed). United States Environmental Protection Agency. Washington, DC. 2009i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7e2a1&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tert-Octyl Mercaptan (Proposed). United States Environmental Protection Agency. Washington, DC. 2008r. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5c7&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Tetramethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-17.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethoxysilane (Proposed). United States Environmental Protection Agency. Washington, DC. 2006i. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d632&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethyl Phosphite (Proposed). United States Environmental Protection Agency. Washington, DC. 2009j. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=0900006480a7d608&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Trimethylacetyl Chloride (Proposed). United States Environmental Protection Agency. Washington, DC. 2008t. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648096e5cc&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for Zinc Phosphide (Proposed). United States Environmental Protection Agency. Washington, DC. 2005e. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020c5ed&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances: Acute Exposure Guideline Levels (AEGLs) for n-Butyl Isocyanate (Proposed). United States Environmental Protection Agency. Washington, DC. 2008m. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=09000064808f9591&disposition=attachment&contentType=pdf. As accessed 2010-08-12.

National Institute for Occupational Safety and Health: NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Cincinnati, OH, 2007.

National Research Council : Acute exposure guideline levels for selected airborne chemicals, 5, National Academies Press, Washington, DC, 2007.

National Research Council: Acute exposure guideline levels for selected airborne chemicals, 6, National Academies Press, Washington, DC, 2008.

National Research Council: Acute exposure guideline levels for selected airborne chemicals, 7, National Academies Press, Washington, DC, 2009.

National Research Council: Acute exposure guideline levels for selected airborne chemicals, 8, National Academies Press, Washington, DC, 2010.

Naysmith A & Robson RH: Focal fits during chlorambucil therapy. Postgrad Med J 1979; 55:806-807.

None Listed: ASHP Therapeutic Guidelines on the Pharmacologic Management of Nausea and Vomiting in Adult and Pediatric Patients Receiving Chemotherapy or Radiation Therapy or Undergoing Surgery. Am J Health Syst Pharm 1999; 56(8):729-764.

None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.

Oppitz MM, Musch E, & Malek M: Studies on the pharmacokinetics of chlorambucil and prednimustine in patients using a new high-performance liquid chromatographic assay. Cancer Chemother Pharmacol 1989; 23:208-212.

Palmer RG, Smith-Burchnell CA, & Dore CJ: Thioguanine-resistant mutations induced by cytotoxic drugs in lymphocytes of patients with connective tissue diseases. Br J Rheumatol 1986; 25:376-379.

Patapanian H, Graham S, & Sambrook PN: The oncogenicity of chlorambucil in rheumatoid arthritis. Br J Rheumatol 1988; 27:44-47.

Peterman A & Braunstein B: Cutaneous reaction to chlorambucil therapy (Letter). Arch Dermatol 1986; 122:1358-1360.

Pieper RO & Erickson LC: DNA adenine adducts induced by nitrogen mustards and their role in transcription termination in vitro. Carcinogenesis 1990; 11:1739-1746.

Pietrantonio F, Moriconi L, & Torino F: Unusual reaction to chlorambucil: a case report. Cancer Lett 1990; 54:109-111.

Polenakovic M & Grcevska L: Development of bronchial adenocarcinoma 11 years after the onset of membranous nephropathy associated with chlorambucil therapy. Nephron 1995; 69:335-336.

Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.

Povirk LF & Shuker DE: DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res 1994; 318:205-226.

Pradhan SN & Marsan CA: Chlorambucil toxicity and EEG "centrecephalic" patterns. Epilepsia 1963; 4:1-14.

Product Information: COMPAZINE(R) tablets, injection, suppositories, syrup, prochlorperazine tablets, injection, suppositories, syrup. GlaxoSmithKline, Research Triangle Park, NC, 2004.

Product Information: Compazine(R), prochlorperazine maleate spansule. GlaxoSmithKline, Research Triangle Park, NC, 2002.

Product Information: LEUKERAN(R) oral tablets, chlorambucil oral tablets. GlaxoSmithKline, Research Triangle Park, NC, 2006.

Product Information: LEUKERAN(R) oral tablets, chlorambucil oral tablets. GlaxoSmithKline (per FDA), Research Triangle Park, NC, 2011.

Product Information: LEUKINE(R) subcutaneous, IV injection, sargramostim subcutaneous, IV injection. Bayer Healthcare, Seattle, WA, 2008.

Product Information: Leukeran(R), chlorambucil. Burroughs Wellcome Co, Research Triangle Park, NC, 1990.

Product Information: NEUPOGEN(R) IV, subcutaneous injection, filgrastim IV, subcutaneous injection. Amgen Manufacturing, Thousand Oaks, CA, 2010.

Product Information: diazepam IM, IV injection, diazepam IM, IV injection. Hospira, Inc (per Manufacturer), Lake Forest, IL, 2008.

Product Information: lorazepam IM, IV injection, lorazepam IM, IV injection. Akorn, Inc, Lake Forest, IL, 2008.

Product Information: promethazine hcl rectal suppositories, promethazine hcl rectal suppositories. Perrigo, Allegan, MI, 2007.

RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 1996; provided by Truven Health Analytics Inc., Greenwood Village, CO.

RTECS : Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety and Health. Cincinnati, OH (Internet Version). Edition expires 1999; provided by Truven Health Analytics Inc., Greenwood Village, CO.

Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.

Reeves BR, Casey G, & Harris H: Long-term cytogenetic follow-up study of patients with uveitis treated with chlorambucil. Carcinogenesis 1985; 6:1615-1619.

Rodriguez-Arnaiz R, Soto PO, & Oyarzun JCG: Analysis of mitotic recombination induced by several mono- and bifunctional alkylating agents in the Drosophila wing-spot test. Mutat Res 1996; 351:133-145.

Rudd P, Fries JF, & Epstein WV: Irreversible bone marrow failure with chlorambucil. J Rheumatol 1975; 2:421-429.

Russell LB, Hunsicker PR, & Cacheiro NL: Chlorambucil effectively induces deletion mutations in mouse germ cells. Proc Natl Acad Sci USA 1989; 86:3704-3708.

Russell LB, Hunsicker PR, & Shelby MD: Chlorambucil and bleomycin induce mutations in the specific-locus test in female mice. Mutat Res 1996; 358:25-35.

Sacanella E, Cervantes F, & Navarro M: Chronic myeloid leukemia after chemotherapy treatment for non-Hodgkin's lymphoma (Spanish). Med Clin (Barc) 1992; 99:145-146.

Salder TW & Kochhar DM: Teratogenic effects of chlorambucil on in vivo and in vitro organogenesis in mice. Teratology 1975; 12:71-78.

Salloum E, Khan KK, & Cooper DL: Chlorambucil-induced seizures. Cancer 1997; 79:1009-1013.

Savolainen HA: Chlorambucil in severe juvenile chronic arthritis: longterm followup with special reference to amyloidosis. J Rheumatol 1999; 26(4):898-903.

Schiffman FJ, Uehara Y, & Fisher JM: Potentiation of chlorambucil activity by phenylbutazone. Cancer Lett 1978; 4:211-216.

Schreiber ZA, Axelrod MR, & Abebe LS: Coexistence of chronic myelogenous leukemia and chronic lymphocytic leukemia. Cancer 1984; 54:697-701.

Scott R, Besag FMC, & Neville BGR: Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomized trial. Lancet 1999; 353:623-626.

Shotton D & Monie IW: Possible teratogenic effect of chlorambucil on a human fetus. JAMA 1963; 186:74.

Singh B & Gupta RS: Comparison of the mutagenic responses of 12 anticancer drugs at the hypoxanthine-guanine phosphoribosyl transferase and adenosine kinase loci in Chinese hamster ovary cells. Environ Mutagen 1983; 5:871-880.

Smith TJ, Khatcheressian J, Lyman GH, et al: 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 24(19):3187-3205.

Sotrel G, Jafari K, & Lash AF: Acute leukemia in advanced ovarian carcinoma after treatment with alkylating agents. Obstet Gynecol 1976; 47:67S-71S.

Speit G, Menz W, & Roescheisen C: Cytogenetic and molecular characterization of the mutagenicity of chlorambucil in V79 cells. Mutat Res 1992; 283:75-81.

Sreenath TG, Gupta P, Sharma KK, et al: Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2010; 14(2):162-168.

Stachowiak J, Gorin NC, & Najman A: Acute leukemia after prolonged treatment with chlorambucil: study of 2 cases. Ann Med Interne Paris 1976; 127:584-589.

Steege JR & Caldwell DS: Renal agenesis after first trimester exposure to chlorambucil. South Med J 1980; 73:1414.

Stevenson AC & Patel C: Effects of chlorambucil on human chromosomes. Mutat Res 1973; 18:333.

Stull DM, Bilmes R, Kim H, et al: Comparison of sargramostim and filgrastim in the treatment of chemotherapy-induced neutropenia. Am J Health Syst Pharm 2005; 62(1):83-87.

Tanaka O, Yoshioka N, & Yoshioka T: Effects of chlorambucil on the brain development in mice during post-neurulation period. Senten Ijo 1991; 31:141-152.

Tripathy NK, Wurgler FE, & Frei H: Genetic toxicity of six carcinogens and six non-carcinogens in the Drosophila wing spot test. Mutat Res 1990; 242:169-180.

U.S. Department of Energy, Office of Emergency Management: Protective Action Criteria (PAC) with AEGLs, ERPGs, & TEELs: Rev. 26 for chemicals of concern. U.S. Department of Energy, Office of Emergency Management. Washington, DC. 2010. Available from URL: http://www.hss.doe.gov/HealthSafety/WSHP/Chem_Safety/teel.html. As accessed 2011-06-27.

U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project : 11th Report on Carcinogens. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Washington, DC. 2005. Available from URL: http://ntp.niehs.nih.gov/INDEXA5E1.HTM?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932. As accessed 2011-06-27.

U.S. Environmental Protection Agency: Discarded commercial chemical products, off-specification species, container residues, and spill residues thereof. Environmental Protection Agency's (EPA) Resource Conservation and Recovery Act (RCRA); List of hazardous substances and reportable quantities 2010b; 40CFR(261.33, e-f):77-.

U.S. Environmental Protection Agency: Integrated Risk Information System (IRIS). U.S. Environmental Protection Agency. Washington, DC. 2011. Available from URL: http://cfpub.epa.gov/ncea/iris/index.cfm?fuseaction=iris.showSubstanceList&list_type=date. As accessed 2011-06-21.

U.S. Environmental Protection Agency: List of Radionuclides. U.S. Environmental Protection Agency. Washington, DC. 2010a. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.

U.S. Environmental Protection Agency: List of hazardous substances and reportable quantities. U.S. Environmental Protection Agency. Washington, DC. 2010. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-sec302-4.pdf. As accessed 2011-06-17.

U.S. Environmental Protection Agency: The list of extremely hazardous substances and their threshold planning quantities (CAS Number Order). U.S. Environmental Protection Agency. Washington, DC. 2010c. Available from URL: http://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol27/pdf/CFR-2010-title40-vol27-part355.pdf. As accessed 2011-06-17.

U.S. Occupational Safety and Health Administration: Part 1910 - Occupational safety and health standards (continued) Occupational Safety, and Health Administration's (OSHA) list of highly hazardous chemicals, toxics and reactives. Subpart Z - toxic and hazardous substances. CFR 2010 2010; Vol6(SEC1910):7-.

U.S. Occupational Safety, and Health Administration (OSHA): Process safety management of highly hazardous chemicals. 29 CFR 2010 2010; 29(1910.119):348-.

United States Environmental Protection Agency Office of Pollution Prevention and Toxics: Acute Exposure Guideline Levels (AEGLs) for Vinyl Acetate (Proposed). United States Environmental Protection Agency. Washington, DC. 2006. Available from URL: http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648020d6af&disposition=attachment&contentType=pdf. As accessed 2010-08-16.

Vandenberg SA, Kulig K, & Spoerke DG: Chlorambucil overdose: accidental ingestion of an antineoplastic drug. J Emerg Med 1988; 6:495-498.

Weber E, Berger S, & Weber S: Rapid desensitization for chlorambucil drug fever. Haematologica 2007; 92(7):e77-.

Westberg NG & Swolin B: Acute myeloid leukemia appearing in two patients after prolonged continuous chlorambucil treatment for Wegener's granulomatosis. Acta Med Scand 1976; 199:373-377.

Westin J: Chromosome abnormalities after chlorambucil therapy of polycythaemia vera. Scand J Haematol 1976; 17:197-204.

Williams SA, Makker SP, & Grupe WE: Seizures: a significant side effect of chlorambucil therapy in children. J Pediatr 1978; 93:516-518.

Witz F, Lederlin P, & Aymard JP: Acute myeloblastic leukemia following chlorambucil treatment: 2 new cases (French). Nouv Presse Med 1978; 7:2392.

Wolfson S & Olney MB: Accidental ingestion of a toxic dose of chlorambucil. JAMA 1957; 239-240.

Woodruff RC, Mason JM, & Valencia R: Chemical mutagenesis testing in Drosophila. V. Results of 53 coded compounds tested for the National Toxicology Program. Environ Mutagen 1985; 7:677-702.

Wyllie ARJ, Bayliff CD, & Kovacs MJ: Myoclonus due to chlorambucil in two adults with lymphoma. Ann Pharmacother 1997; 31:171-174.

Yamada M, Sofuni T, & Nohmi T: Preferential induction of AT-TA transversion, but not deletions, by chlorambucil at the hisG428 site of Salmonella typhimurium TA102. Mutat Res 1992; 283:29-33.

Yiannakis PH & Larner AJ: Visual failure and optic atrophy associated with chlorambucil therapy. Br Med J 1993; 306:109.

FeedBack

CHLORAMBUCIL

Classification | Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents