NITROFURANTOIN AND RELATED AGENTS

Nitrofurantoin is used to prevent and treat urinary tract infections due to susceptible strains of Escherichia coli, enterococci, Staphylococcus aureus and some strains of Klebsiella and Enterobacter. It is not indicated for the treatment of pyelonephritis or perinephric abscess (Prod Info Macrodantin(R) oral capsule, 2011; Prod Info Macrobid(R) oral capsule, 2011; Prod Info nitrofurantoin oral capsules, 2006).
Nitrofurazone, a nitrofuran derivative, was used as an anti-infective agent for burns (as adjunctive therapy for second- and third-degree burns) and for the preparation of surfaces before skin grafting (Prod Info Furacin(R), 1994). It is no longer available in the United States.

FORMS

Macrobid(R) (nitrofurantoin monohydrate/macrocrystals) is available in the US as 100 mg capsules (Prod Info Macrobid(R) oral capsule, 2011). Macrodantin(R) (nitrofurantoin macrocrystals) is available in the US as 25 mg, 50 mg, and 100 mg capsules (Prod Info Macrodantin(R) oral capsule, 2011). Nitrofurantoin generic is available as oral suspension (25 mg/5 mL) and 100 mg tablets (Prod Info nitrofurantoin oral capsules, 2006). Furadantin(R) is available as oral suspension (25 mg/5 mL) (Prod Info FURADANTIN(R) oral suspension, 2008).
Nitrofurazone was available in the US as 0.2% topical ointment (Prod Info Furacin(R), 1994). It is no longer available in the United States.

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Nitrofurantoin is used to prevent and treat urinary tract infections due to susceptible strains of Escherichia coli, enterococci, Staphylococcus aureus and some strains of Klebsiella and Enterobacter. It is not indicated for the treatment of pyelonephritis or perinephric abscess. Nitrofurantoin is also available as nitrofurantoin macrocrystals and nitrofurantoin monohydrate/nitrofurantoin, macrocrystals.

PHARMACOLOGY: Nitrofurantoin is bactericidal at therapeutic doses. Through its reactive intermediates, it inactivates bacterial ribosomal proteins and other large molecules resulting in inhibition of vital biochemical processes such as protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis.

EPIDEMIOLOGY: Overdose is rare.

WITH POISONING/EXPOSURE

There are very little data available on toxicity of nitrofurantoin after an overdose. Acute overdose has resulted in only vomiting.

WITH THERAPEUTIC USE

COMMON: Nausea, vomiting, anorexia, headache. OTHER EFFECTS: Diarrhea, abdominal pain, constipation, dyspepsia.
PULMONARY HYPERSENSITIVITY REACTION: Acute, subacute or chronic pulmonary hypersensitivity reactions have rarely occurred; fatalities have been reported. Pulmonary toxicity may include diffuse interstitial pneumonitis, pulmonary fibrosis, or both. Patients receiving long-term treatment for 6 months or longer are at increased risk of developing chronic pulmonary reactions. Acute pulmonary reactions usually occur within the first week of treatment, and can be manifested by eosinophilia, fever, chills, cough, chest pain, dyspnea, or pulmonary infiltration with consolidation or pleural effusion on x-ray. Eosinophilia and fever occur less frequently in subacute pulmonary reactions than in the acute form. Recovery may vary from dramatic resolution to several months. Patients with pulmonary reactions have also developed ECG changes (eg, non-specific ST/T wave changes, bundle branch block).
RARE: Erythema multiforme, Stevens-Johnson syndrome, maculopapular or macular rashes, fixed drug reactions, erythema nodosum, angioedema, bullous eruptions, immune hypersensitivity reactions, nystagmus, papilledema, elevated liver enzymes, cholestatic hepatitis, peripheral neuropathy, neutropenia, leukopenia, granulocytopenia, hemolytic anemia (linked to G6PD deficiency), megaloblastic anemia, agranulocytosis, methemoglobinemia, Lyell's syndrome, and SLE syndromes. Peripheral neuropathy has occurred following nitrofurantoin therapy. Some cases may become severe, irreversible, or fatal. Renal impairment, anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, or debilitating disease may increase the risk for peripheral neuropathy.

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

ACUTE CLINICAL EFFECTS

SUMMARY

PHARMACOLOGY: Nitrofurantoin is bactericidal at therapeutic doses. Through its reactive intermediates, it inactivates bacterial ribosomal proteins and other large molecules resulting in inhibition of vital biochemical processes such as protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis.
EPIDEMIOLOGY: Overdose is rare.
THERAPEUTIC

COMMON: Nausea, vomiting, anorexia, headache. OTHER EFFECTS: Diarrhea, abdominal pain, constipation, dyspepsia.
PULMONARY HYPERSENSITIVITY REACTION: Acute, subacute or chronic pulmonary hypersensitivity reactions have rarely occurred; fatalities have been reported. Pulmonary toxicity may include diffuse interstitial pneumonitis, pulmonary fibrosis, or both. Patients receiving long-term treatment for 6 months or longer are at increased risk of developing chronic pulmonary reactions. Acute pulmonary reactions usually occur within the first week of treatment, and can be manifested by eosinophilia, fever, chills, cough, chest pain, dyspnea, or pulmonary infiltration with consolidation or pleural effusion on x-ray. Eosinophilia and fever occur less frequently in subacute pulmonary reactions than in the acute form. Recovery may vary from dramatic resolution to several months. Patients with pulmonary reactions have also developed ECG changes (eg, non-specific ST/T wave changes, bundle branch block).
RARE: Erythema multiforme, Stevens-Johnson syndrome, maculopapular or macular rashes, fixed drug reactions, erythema nodosum, angioedema, bullous eruptions, immune hypersensitivity reactions, nystagmus, papilledema, elevated liver enzymes, cholestatic hepatitis, peripheral neuropathy, neutropenia, leukopenia, granulocytopenia, hemolytic anemia (linked to G6PD deficiency), megaloblastic anemia, agranulocytosis, methemoglobinemia, Lyell's syndrome, and SLE syndromes. Peripheral neuropathy has occurred following nitrofurantoin therapy. Some cases may become severe, irreversible, or fatal. Renal impairment, anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, or debilitating disease may increase the risk for peripheral neuropathy.

OVERDOSE

There are very little data available on toxicity of nitrofurantoin after an overdose. Acute overdose has resulted in only vomiting.

CARDIOVASCULAR

ECG ABNORMALITIES: Patients with pulmonary reactions have developed ECG changes (eg, non-specific ST/T wave changes, bundle branch block) (Prod Info Macrobid(R) oral capsule, 2011; Prod Info Macrodantin(R) oral capsule, 2011).

DERMATOLOGIC

ERYTHEMA MULTIFORME, CASE REPORT: Drug-induced lupus erythematosus with an erythematous skin rash was described in a 66-year-old female following intermittent therapeutic use of nitrofurantoin (Chapman, 1986).
STEVENS-JOHNSON SYNDROME: Stevens-Johnson syndrome has rarely occurred following nitrofurantoin monohydrate/macrocrystals therapy in clinical trials (Prod Info Macrobid(R) oral capsule, 2011).
HYPERSENSITIVITY: In postmarketing surveillance worldwide, immune hypersensitivity reactions represent the most frequent spontaneously-reported adverse reactions with the use of nitrofurantoin (Prod Info Macrobid(R) oral capsule, 2011). Maculopapular or macular rashes, fixed drug reactions, erythema nodosum, angioedema, bullous eruptions, Lyell's syndrome and SLE syndromes have been seen with therapeutic use (Shah & Wade, 1989).

GASTROINTESTINAL

The most common adverse effects are nausea, vomiting, and anorexia. Less common effects include abdominal pain diarrhea, dyspepsia, and constipation (Prod Info Macrodantin(R) oral capsule, 2011; Prod Info Macrobid(R) oral capsule, 2011). The incidence during therapeutic use with microcrystals was approximately 30%, using the macrocrystals it has been reduced approximately 1/2 (D'Archy, 1985).
NAUSEA: Nausea has occurred in 8% of patients following nitrofurantoin monohydrate/macrocrystals therapy in clinical trials, possibly or probably related to the drug (Prod Info Macrobid(R) oral capsule, 2011).
VOMITING: Acute overdose has resulted in only vomiting (Prod Info Macrobid(R) oral capsule, 2011).

GENITOURINARY

CRYSTALLURIA, CASE REPORTS: Small irregular purple crystals were found in the urine of 3 elderly patients with urinary catheters following prophylactic nitrofurantoin therapy for 1.5 to 3 months (Macdonald & Macdonald, 1976).

HEENT

NYSTAGMUS: Nystagmus has occurred following nitrofurantoin monohydrate/macrocrystals therapy in clinical trials (Prod Info Macrobid(R) oral capsule, 2011).

HEMATOLOGIC

AGRANULOCYTOSIS: Leukopenia, granulocytopenia, hemolytic anemia, megaloblastic anemia, and agranulocytosis have been reported with nitrofurantoin use (D'Archy, 1985). These effects occurred following nitrofurantoin monohydrate/macrocrystals therapy in clinical trials, regardless of causality relationship to the drug. In most cases, the hematologic abnormality resolved following discontinuation of therapy (Prod Info Macrobid(R) oral capsule, 2011).
ANEMIA: Anemia has been more frequently seen in patients with either G6PD, enolase, or glutathione peroxidase deficiency (D'Archy, 1985; Steinberg et al, 1970).
METHEMOGLOBINEMIA: Methemoglobinemia has rarely been reported with nitrofurantoin therapy (Coraggio et al, 1989). Rare cases of cyanosis secondary to methemoglobinemia has been reported (Prod Info Macrobid(R) oral capsule, 2011).
NEUTROPENIA: Neutropenia has rarely been reported with nitrofurantoin therapy (Coraggio et al, 1989).
HEMOLYTIC ANEMIA: Hemolytic anemia of the primaquine-sensitivity type has occurred following nitrofurantoin monohydrate/macrocrystals therapy. Most cases appeared to be linked to a glucose-6-phosphate dehydrogenase (G6PD) deficiency. Hemolysis stopped when the nitrofurantoin was withdrawn (Prod Info Macrobid(R) oral capsule, 2011). Two cases of hemolytic anemia are reported in children with probable glucose-6-phosphate dehydrogenase deficiency (Coraggio et al, 1989).

HEPATIC

HEPATOTOXICITY: Cholestatic jaundice has rarely occurred following nitrofurantoin monohydrate/macrocrystals therapy in clinical trials; however, fatalities have been reported (Prod Info Macrobid(R) oral capsule, 2011). Several cases of both hepatic and pulmonary toxicity have been described following chronic therapy in elderly patients (Kelly et al, 1998; Schattner et al, 1999). Symptoms of hepatotoxicity can begin within 1 to 6 weeks of the start of therapy, presenting with jaundice, abdominal pain, malaise, nausea, eosinophilia, and anorexia (Shah & Wade, 1989; Sharp et al, 1980).
PEDIATRIC HEPATOTOXICITY: Hepatic toxicity, including focal nodular hyperplasia, anicteric hepatitis, cholestatic hepatitis, and chronic active hepatitis have been reported in children (Coraggio et al, 1989).
LIVER ENZYME ABNORMALITIES: Elevations of alkaline phosphatase and aspartate transaminase have occurred during therapeutic use of nitrofurantoin (Thomson & James, 1986).

IMMUNOLOGIC

In postmarketing surveillance worldwide, immune hypersensitivity reactions represent the most frequent spontaneously-reported adverse reactions with the use of nitrofurantoin (Prod Info Macrobid(R) oral capsule, 2011).
Maculopapular or macular rashes, fixed drug reactions, erythema nodosum, angioedema, bullous eruptions, Lyell's syndrome and SLE syndromes have been seen with therapeutic use (Shah & Wade, 1989).

NEUROLOGIC

HEADACHE: Headache has occurred in 6% of patients following nitrofurantoin monohydrate/macrocrystals therapy in clinical trials (Prod Info Macrobid(R) oral capsule, 2011).
PERIPHERAL NEUROPATHY: Peripheral neuropathy has occurred following nitrofurantoin monohydrate/macrocrystals therapy. Some cases may become severe, irreversible, or fatal. Renal impairment (creatinine clearance under 60 milliliter/minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, or debilitating disease may increase the risk for peripheral neuropathy (Prod Info Macrobid(R) oral capsule, 2011).
Symptoms are essentially distal, usually affecting primarily the legs, but hands may also be involved. Sensory symptoms of burning, painful feet and distal motor weakness may be noted (Cavanagh, 1973).

RESPIRATORY

PULMONARY TOXICITY: Acute, subacute or chronic pulmonary reactions have rarely occurred following nitrofurantoin monohydrate/macrocrystals therapy in clinical trials; however, fatalities have been reported. Pulmonary toxicity may include diffuse interstitial pneumonitis, pulmonary fibrosis, or both. Patients receiving long-term treatment for 6 months or longer are at increased risk of developing chronic pulmonary reactions. Acute pulmonary reactions usually occur within the first week of treatment, and can be manifested by eosinophilia, fever, chills, cough, chest pain, dyspnea, or pulmonary infiltration with consolidation or pleural effusion on x-ray. Eosinophilia and fever occur less frequently in subacute pulmonary reactions than in the acute form. Recovery may vary from dramatic resolution to several months (Prod Info Macrobid(R) oral capsule, 2011).
Characteristic effects of acute pulmonary toxicity after therapeutic use include: bronchospasm or a hypersensitivity syndrome of dyspnea, nonproductive cough, fever, elevated erythrocyte sedimentation rate, eosinophilia, and chest pain (Chudnofsky & Otten, 1989; Schattner et al, 1999). Symptoms can range from mild dyspnea to noncardiogenic pulmonary edema (Chudnofsky & Otten, 1989).
ONSET: Symptoms have been reported as early as several hours after the start of therapy, and most often occur within the first 3 weeks of administration (Chudnofsky & Otten, 1989; Schattner et al, 1999).
INCIDENCE: Pulmonary effects have been reported to occur in 12.5% to 43% of patients reporting an adverse response to nitrofurantoin; however, the actual incidence is only 1 of 476,190 courses of therapy (Chudnofsky & Otten, 1989).
OUTCOME: In most cases symptoms resolve within 24 hours of drug cessation (Chudnofsky & Otten, 1989).
CHRONIC TOXICITY: Pulmonary toxicity is a rare (0.0013% of therapeutic courses) occurrence of nitrofurantoin therapy (Schattner et al, 1999). ONSET: toxicity can develop up to 5 years after exposure with a slow and gradual onset of symptoms (Schattner et al, 1999).

VITAL SIGNS

FEVER AND CHILLS: Both fever and chills have been reported with therapy (Prod Info Macrobid(R) oral capsule, 2011).

CHRONIC CLINICAL EFFECTS

WITH THERAPEUTIC USE

Nitrofurantoin is a sensitizer. Hypersensitivity reactions may affect the lungs, liver, or blood, producing chills, fever, leukopenia, granulopenia, jaundice, and liver damage (Gilman et al, 1990).
Allergic skin reactions have also occurred; these may take the form of a diffuse, erythematous, maculopapular rash, urticaria, eczemoid rash, or pruritus (Gleckman et al, 1979). Severe itching, burning, and tearing of the eyes may persist for weeks after cessation of use of the medication. Nonfatal anaphylactic reactions have also been reported (Tykal & Wilms, 1972; Satter, 1966).
Allergic pneumonitis has been reported in several elderly patients chronically using nitrofurantoin (Rosenow et al, 1968). This reaction may be both dose-related and allergic in nature (Boyd et al, 1979; Shah & Wade, 1989).
Pulmonary fibrosis, which may be of an allergic nature, has developed in several patients after years of therapy (Jayasundera et al, 1980; Robinson et al, 1980; Wilcox et al, 1982). The disease may have a slow and insidious onset, with progressive shortness of breath and productive or non-productive cough. Discontinuation of the drug may allow improvement.
Nitrofurantoin has been linked with autoimmune conditions including chronic active hepatitis and systemic lupus erythematosus (Ernaelsteen & Williams, 1961; Holmberg et al, 1980) Zimmerman, 1978; (Stromberg & Wengle, 1976; Filipek, 1979; Chapman, 1986). Chronic liver toxicity usually develops within 6 months of initiation of therapy (Stricker et al, 1988). It may have an insidious onset (Stromberg & Wengle, 1976).
Nitrofurantoin-induced hypersensitivity hepatitis recurred as long as 17 years after the initial appearance in one case; rechallenge with the drug provoked a severe hepatic reaction (Paiva et al, 1992). There is another case of both hepatitis and neurologic effects (seventh cranial nerve palsy) developing after repeated treatment (Thomson & James, 1986). There were also simultaneous occurrences of both chronic hepatitis and pulmonary fibrosis in another nitrofurantoin-treated patient (Reinhart et al, 1992).
Fever, rash, eosinophilia, elevated creatinine, hematuria, macropapular rash, proteinuria, and sterile pyuria led to a diagnosis of acute interstitial nephritis (AIN) in a 68-year-old man who had received 200 mg/day of nitrofurantoin for 14 days for treatment of prostatitis. Neutrophilia and eosinophilia were also present. All abnormalities resolved after discontinuation of the medication. This is the first report of AIN which is clearly attributable to nitrofurantoin (Kahn, 1996).

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

PREHOSPITAL: Gastrointestinal decontamination is not routinely required.

-MEDICAL TREATMENT

LIFE SUPPORT

Support respiratory and cardiovascular function.

SUMMARY

FIRST AID

PREHOSPITAL: Gastrointestinal decontamination is not routinely required. Treatment is symptomatic and supportive.

-RANGE OF TOXICITY

MINIMUM LETHAL EXPOSURE

GENERAL/SUMMARY

Acute overdose has resulted in only vomiting (Prod Info Macrobid(R) oral capsule, 2011). No doses were provided.
ANIMAL STUDIES: In animal tests, mice succumbed to 100 milligrams/kilogram (Gosselin et al, 1984).

MAXIMUM TOLERATED EXPOSURE

Carcinogenicity Ratings for CAS67-20-9 :

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): 3 ; Listed as: Nitrofurantoin

3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.

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 CAS67-20-9 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

LD50- (INTRAPERITONEAL)MOUSE:
- 150 mg/kg
LD50- (ORAL)MOUSE:
- 360 mg/kg
LD50- (INTRAPERITONEAL)RAT:
- 112 mg/kg
LD50- (ORAL)RAT:
- 604 mg/kg

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS67-20-9 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS67-20-9 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS67-20-9 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS67-20-9 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS67-20-9 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS67-20-9 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS67-20-9 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS67-20-9 (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 CAS67-20-9 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS67-20-9 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS67-20-9 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS67-20-9 (EPA, 2005):

Listed as: 2,4-Imidazolidinedione, 1-[[(5-nitro-2-furanyl)methylene]amino]-

LABELS

NFPA

NFPA Hazard Ratings for CAS67-20-9 (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 67-20-9.

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 CAS67-20-9 (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 CAS67-20-9 (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 CAS67-20-9 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS67-20-9 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS67-20-9 (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 CAS67-20-9 (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

238.16 (Budavari, 1996).

DESCRIPTION/PHYSICAL STATE

Nitrofurantoin is odorless with a bitter taste.

SOLUBILITY

IN WATER

19 mg/100 mL (at pH 7)

OTHER/PHYSICAL

DISSOCIATION CONSTANT

pKa = 7.2 (Shah & Wade, 1989)

-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.

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Information to evaluate chemical incidents