AMINOPTERIN
HAZARDTEXT ®
Information to help in the initial response for evaluating chemical incidents
-IDENTIFICATION
SYNONYMS
Aminopteridine A-ninopterin APGA ENT 26,079 NSC 739 4-Aminopteroylglutamic acid 4-Aminopteroylglutamate N-(4-(2,4-Diaminopteridin-6-ylmethyl)amino)benzoyl-L(+)-glytamic acid Molecular Formula: C19-H20-N8-O5 CAS 54-62-6
IDENTIFIERS
Editor's Note: This material is not listed in the Emergency Response Guidebook. Based on the material's physical and chemical properties, toxicity, or chemical group, a guide has been assigned. For additional technical information, contact one of the emergency response telephone numbers listed under Public Safety Measures.
SYNONYM REFERENCE
- (RTECS , 1991; EPA, 1985; Sax & Lewis, 1987)
USES/FORMS/SOURCES
RODENTICIDE - U.S. patent to American Cyanamid (Windholz, 1983) Aminopterin was being investigated as a potential form of treatment for acute leukemia in children (Sollman, 1957). In 1985, aminopterin was removed from the National Cancer Institute's list of investigational drugs.
-CLINICAL EFFECTS
GENERAL CLINICAL EFFECTS
- Aminopterin is a folic acid antagonist, structurally similar to methotrexate. Bone marrow hypoplasia, nausea, vomiting, anorexia and fetal death or abnormalities may occur with aminopterin overdose.
- Aminopterin is structurally related to methotrexate and might produce similar toxic effects.
- POTENTIAL HEALTH HAZARDS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
Highly toxic, may be fatal if inhaled, swallowed or absorbed through skin. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution.
ACUTE CLINICAL EFFECTS
- Acute exposure would be expected to cause acute gastrointestinal distress, including nausea and vomiting. It is possible, although not proven, that all or some of the effects seen with repeated therapeutic exposure may occur with high-level acute exposure.
CHRONIC CLINICAL EFFECTS
- Upset stomach, nausea, and vomiting were observed during therapeutic clinical trials (Farber et al, 1948; Stickney et al, 1948). Gastrointestinal hemorrhage and deafness occurred in some patients (Stickney et al, 1948).
- Bone marrow suppression was seen in therapeutic clinical trials (Phillips & Thiersch, 1949). Bone marrow returned to normal within about 18 days after cessation of treatment (Thiersch, 1949).
- Alopecia has occurred in patients receiving aminopterin (Stickney et al, 1948; Karnofsky et al, 1950).
-FIRST AID
FIRST AID AND PREHOSPITAL TREATMENT
-MEDICAL TREATMENT
LIFE SUPPORT
- Support respiratory and cardiovascular function.
SUMMARY
- FIRST AID - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
Move victim to fresh air. Call 911 or emergency medical service. Give artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance;give artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. For minor skin contact, avoid spreading material on unaffected skin. Keep victim warm and quiet. Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed. Ensure that medical personnel are aware of the material(s) involved and take precautions to protect themselves.
ORAL EXPOSURE ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
EYE EXPOSURE DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
DERMAL EXPOSURE
-RANGE OF TOXICITY
MINIMUM LETHAL EXPOSURE
MAXIMUM TOLERATED EXPOSURE
The maximum tolerated human exposure to this agent has not been delineated. Small doses may result in some aplasia of bone marrow (Sollman, 1957). In one study, the maximum tolerated dose was 2 milligram/meter squared every 12 hours for two doses weekly with a leucovorin rescue of 5 milligrams/meter squared orally every 12 hours for two doses, starting 24 hours after the second dose of aminopterin (Ratliff et al, 1998). The dose limiting symptom is mucosal toxicity (Ratliff et al, 1998).
- Carcinogenicity Ratings for CAS54-62-6 :
ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed EPA (U.S. Environmental Protection Agency, 2011): Not Listed IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed MAK (DFG, 2002): Not Listed NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed
TOXICITY AND RISK ASSESSMENT VALUES
- EPA Risk Assessment Values for CAS54-62-6 (U.S. Environmental Protection Agency, 2011):
References: RTECS, 2002 LD50- (INTRAPERITONEAL)MOUSE: LD50- (ORAL)MOUSE: LD50- (INTRAPERITONEAL)RAT: LDLo- (ORAL)RAT: TDLo- (ORAL)DOG: TDLo- (ORAL)HUMAN: TDLo- (INTRAPERITONEAL)MOUSE: TDLo- (ORAL)PIG: TDLo- (INTRAPERITONEAL)RAT:
-STANDARDS AND LABELS
WORKPLACE STANDARDS
- ACGIH TLV Values for CAS54-62-6 (American Conference of Governmental Industrial Hygienists, 2010):
- AIHA WEEL Values for CAS54-62-6 (AIHA, 2006):
- NIOSH REL and IDLH Values for CAS54-62-6 (National Institute for Occupational Safety and Health, 2007):
- OSHA PEL Values for CAS54-62-6 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
- OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS54-62-6 (U.S. Occupational Safety and Health Administration, 2010):
ENVIRONMENTAL STANDARDS
- EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS54-62-6 (U.S. Environmental Protection Agency, 2010):
- EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS54-62-6 (U.S. Environmental Protection Agency, 2010):
- EPA RCRA Hazardous Waste Number for CAS54-62-6 (U.S. Environmental Protection Agency, 2010b):
- EPA SARA Title III, Extremely Hazardous Substance List for CAS54-62-6 (U.S. Environmental Protection Agency, 2010):
Listed as: Aminopterin Reportable Quantity, in pounds: 500 Threshold Planning Quantity, in pounds: Note(s): Not Listed
- EPA SARA Title III, Community Right-to-Know for CAS54-62-6 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):
- DOT List of Marine Pollutants for CAS54-62-6 (49 CFR 172.101 - App. B, 2005):
- EPA TSCA Inventory for CAS54-62-6 (EPA, 2005):
SHIPPING REGULATIONS
- DOT -- Table of Hazardous Materials and Special Provisions (49 CFR 172.101, 2005):
- ICAO International Shipping Name (ICAO, 2002):
LABELS
- NFPA Hazard Ratings for CAS54-62-6 (NFPA, 2002):
-PERSONAL PROTECTION
SUMMARY
- RECOMMENDED PROTECTIVE CLOTHING - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible.
- No specific measures or clothing has been recommended. This compound is highly toxic by ingestion, so full protective clothing and a self-contained positive pressure breathing apparatus should be worn.
RESPIRATORY PROTECTION
- Refer to "Recommendations for respirator selection" in the NIOSH Pocket Guide to Chemical Hazards on TOMES Plus(R) for respirator information.
PROTECTIVE CLOTHING
- CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 54-62-6.
-PHYSICAL HAZARDS
FIRE HAZARD
Editor's Note: This material is not listed in the Emergency Response Guidebook. Based on the material's physical and chemical properties, toxicity, or chemical group, a guide has been assigned. For additional technical information, contact one of the emergency response telephone numbers listed under Public Safety Measures. POTENTIAL FIRE OR EXPLOSION HAZARDS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004) Non-combustible, substance itself does not burn but may decompose upon heating to produce corrosive and/or toxic fumes. Containers may explode when heated. Runoff may pollute waterways.
- FLAMMABILITY CLASSIFICATION
- NFPA Flammability Rating for CAS54-62-6 (NFPA, 2002):
- FIRE CONTROL/EXTINGUISHING AGENTS
- SMALL FIRE PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
- LARGE FIRE PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
Water spray, fog or regular foam. Move containers from fire area if you can do it without risk. Dike fire control water for later disposal; do not scatter the material. Use water spray or fog; do not use straight streams.
- TANK OR CAR/TRAILER LOAD FIRE PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire. For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire burn.
- NFPA Extinguishing Methods for CAS54-62-6 (NFPA, 2002):
REACTIVITY HAZARD
- INVESTIGATIONAL DRUG PRODUCT: In intact vial, is stable for at least 6 years when stored under refrigeration at 2 to 8 degrees C.
EVACUATION PROCEDURES
- Editor's Note: This material is not listed in the Table of Initial Isolation and Protective Action Distances.
- SPILL - PUBLIC SAFETY EVACUATION DISTANCES - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
Increase, in the downwind direction, as necessary, the isolation distance of at least 25 to 50 meters (80 to 160 feet) in all directions.
- FIRE - PUBLIC SAFETY EVACUATION DISTANCES - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions.
- PUBLIC SAFETY MEASURES - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004)
CALL Emergency Response Telephone Number on Shipping Paper first. If Shipping Paper not available or no answer, refer to appropriate telephone number: MEXICO: SETIQ: 01-800-00-214-00 in the Mexican Republic; For calls originating in Mexico City and the Metropolitan Area: 5559-1588; For calls originating elsewhere, call: 011-52-555-559-1588.
CENACOM: 01-800-00-413-00 in the Mexican Republic; For calls originating in Mexico City and the Metropolitan Area: 5550-1496, 5550-1552, 5550-1485, or 5550-4885; For calls originating elsewhere, call: 011-52-555-550-1496, or 011-52-555-550-1552; 011-52-555-550-1485, or 011-52-555-550-4885.
ARGENTINA: CIQUIME: 0-800-222-2933 in the Republic of Argentina; For calls originating elsewhere, call: +54-11-4613-1100.
BRAZIL: PRÓ-QUÍMICA: 0-800-118270 (Toll-free in Brazil); For calls originating elsewhere, call: +55-11-232-1144 (Collect calls are accepted).
COLUMBIA: CISPROQUIM: 01-800-091-6012 in Colombia; For calls originating in Bogotá, Colombia, call: 288-6012; For calls originating elsewhere, call: 011-57-1-288-6012.
CANADA: UNITED STATES:
For additional details see the section entitled "WHO TO CALL FOR ASSISTANCE" under the ERG Instructions. As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. Keep unauthorized personnel away. Stay upwind. Keep out of low areas.
- AIHA ERPG Values for CAS54-62-6 (AIHA, 2006):
- DOE TEEL Values for CAS54-62-6 (U.S. Department of Energy, Office of Emergency Management, 2010):
Listed as Aminopterin (Aminopteridine) TEEL-0 (units = mg/m3): 5 TEEL-1 (units = mg/m3): 15 TEEL-2 (units = mg/m3): 25 TEEL-3 (units = mg/m3): 25 Definitions: TEEL-0: The threshold concentration below which most people will experience no adverse health effects. TEEL-1: The airborne concentration (expressed as ppm [parts per million] or mg/m(3) [milligrams per cubic meter]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. However, these effects are not disabling and are transient and reversible upon cessation of exposure. TEEL-2: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience irreversible or other serious, long-lasting, adverse health effects or an impaired ability to escape. TEEL-3: The airborne concentration (expressed as ppm or mg/m(3)) of a substance above which it is predicted that the general population, including susceptible individuals, could experience life-threatening adverse health effects or death.
- AEGL Values for CAS54-62-6 (National Research Council, 2010; National Research Council, 2009; National Research Council, 2008; National Research Council, 2007; NRC, 2001; NRC, 2002; NRC, 2003; NRC, 2004; NRC, 2004; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 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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; 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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):
- NIOSH IDLH Values for CAS54-62-6 (National Institute for Occupational Safety and Health, 2007):
CONTAINMENT/WASTE TREATMENT OPTIONS
SPILL OR LEAK PRECAUTIONS - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004) Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Cover with plastic sheet to prevent spreading. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS.
RECOMMENDED PROTECTIVE CLOTHING - EMERGENCY RESPONSE GUIDEBOOK, GUIDE 151 (ERG, 2004) Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible.
Use a water spray to reduce any vapors (EPA, 1985).
-ENVIRONMENTAL HAZARD MANAGEMENT
POLLUTION HAZARD
- This compound is toxic to a wide variety of species and is used as a rodenticide.
ABIOTIC DEGRADATION
- No information found at the time of this review.
ENVIRONMENTAL TOXICITY
- No information found at the time of this review.
-PHYSICAL/CHEMICAL PROPERTIES
MOLECULAR WEIGHT
- 440.47 (EPA, 1985) Reynolds, 1988)
DESCRIPTION/PHYSICAL STATE
- Aminopterin occurs as orange-yellow powder or as clusters of yellow, needle-shaped crystals (Reynolds, 1988; (EPA, 1985).
PH
- 6.5-8.5 (INVESTIGATIONAL DRUG PRODUCT, reconstituted solution)
SOLUBILITY
-REFERENCES
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- 40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.
- 49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.
- 49 CFR 172.101: Department of Transportation - Table of Hazardous Materials. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 11, 2005.
- 62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.
- 65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
- 65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
- 65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.
- 66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.
- 67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.
- 68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.
- 69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.
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