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Phthalazine, 1 - hydrazino -

RTECS #: TH8925000

CAS #: 86-54-4

UPDATE: May 2009 MW: 160.20 MF: C8H8N4


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. MUTATION DATA:
  3. REPRODUCTIVE EFFECTS DATA:
  4. TUMORIGENIC DATA:
  5. ACUTE TOXICITY DATA:
  6. OTHER MULTIPLE DOSE DATA:
  7. REVIEWS:
  8. NIOSH DOCUMENTATION AND SURVEILLANCE:
  9. REFERENCES:

SYNONYMS:

  1. 1 (2H) - Phthalazinone hydrazone
  2. 1 - Hydrazinophthalazine
  3. Apresolin
  4. Apresoline
  5. Apressin
  6. Aprezolin
  7. BA 5968
  8. C 5968
  9. Ciba 5968
  1. Hidralazin
  2. Hidralazina (Spanish)
  3. Hipoftalin
  4. Hydralazin
  5. Hydralazine
  6. Hydrazinophthalazine
  7. Hypophthalin
  8. Idralazina (Italian)


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
N/R
 N/R N/R N/R


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
DNA repair Escherichia coli 200 µg/disc MUREAV 68,79,1979
unscheduled DNA synthesis rabbit liver 5 mmol/L PNASA6 79,1269,1982
mutation in microorganisms Salmonella typhimurium 500 µg/plate (+enzymatic activation step) MUREAV 68,79,1979
mutation in mammalian somatic cells rat liver 5 µmol/L TXAPA9 118,135,1993
specific locus test oral
Drosophila melanogaster 		200 mmol/L/6 hour MUREAV 120,233,1983


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
woman 		lowest published toxic dose: 7 mg/kg (34-35 week pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system AJOGAH 160,105,1989
unreported route
rat 		lowest published toxic dose: 330 mg/kg (1-22 day pregnant) Reproductive: Effects on newborn: Weaning or lactation index (e.g., # alive at weaning per # alive at day 4) ANREAK 193,174,1979
unreported route
woman 		lowest published toxic dose: 54 mg/kg (26-39 week pregnant) Reproductive: Specific developmental abnormalities: Blood and lymphatic systems (including spleen and marrow) NEJMAG 303,1235,1980


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 45,427 mg/kg/2 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		EXPADD 32,119,1987


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intramuscular
man 		lowest published toxic dose: 89 µg/kg Cardiac: Cardiomyopathy including infarction

Cardiac: Changes in coronary arteries 		EJPEDT 145,318,1986
intraperitoneal
mouse 		lethal dose (50 percent kill): 80 mg/kg N/R PCJOAU 30,22,1996
intraperitoneal
rat 		lethal dose (50 percent kill): 25 mg/kg N/R JPETAB 143,7,1964
intravenous
cat 		lowest published toxic dose: 1 mg/kg Vascular: BP lowering not characterized in autonomic section

Vascular: Regional or general arteriolar or venous dilation 		FATOAO 44,181,1981
intravenous
dog 		lethal dose (50 percent kill): 50 mg/kg N/R ARZNAD 35,818,1985
intravenous
mouse 		lethal dose (50 percent kill): 52 mg/kg N/R MDACAP 12,468,1976
intravenous
rat 		lethal dose (50 percent kill): 34 mg/kg Cardiac: Change in rate

Behavioral: Somnolence (general depressed activity)

Gastrointestinal: Nausea or vomiting 		JAPMA8 40,559,1951
intravenous
rat 		lowest published toxic dose: 3 mg/kg Vascular: BP lowering not characterized in autonomic section FCLPH* 17,315,2003
oral
dog 		lethal dose (50 percent kill): 100 mg/kg N/R ARZNAD 23,1591,1973
oral
guinea pig 		lethal dose (50 percent kill): 250 mg/kg N/R BCFAAI 111,480,1972
oral
man 		lowest published toxic dose: 2,086 mg/kg/2 year- intermittent Skin: After systemic exposure: Dermatitis, allergic BMJOAE 289,410,1984
oral
mouse 		lethal dose (50 percent kill): 122 mg/kg N/R PLRCAT 8,295,1976
oral
rat 		lethal dose (50 percent kill): 90 mg/kg Cardiac: Pulse rate increased without fall in BP

Vascular: BP lowering not characterized in autonomic section 		PLRCAT 8,295,1976
oral
rabbit 		lethal dose (50 percent kill): 300 mg/kg N/R ARZNAD 23,1591,1973
oral
woman 		lowest published toxic dose: 730 mg/kg/2 year- intermittent Skin: After systemic exposure: Dermatitis, allergic BMJOAE 289,410,1984
subcutaneous
mouse 		lethal dose (50 percent kill): 150 mg/kg N/R RPTOAN 31,53,1968
subcutaneous
mouse 		lowest published toxic dose: 40 mg/kg Immunological Including Allergic: Increase in humoral response TXCYAC 200,247,2004


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
rat 		lowest published toxic dose: 3,600 mg/kg/5 week- intermittent Blood: Normocytic anemia

Blood: Changes in other cell count (unspecified)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		TXAPA9 44,431,1978
oral
rat 		lowest published toxic dose: 9,360 mg/kg/26 week- intermittent Blood: Normocytic anemia

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		TXAPA9 44,431,1978
oral
rat 		lowest published toxic dose: 70 mg/kg/1 week- intermittent Vascular: BP lowering not characterized in autonomic section JPETAB 294,948,2000
oral
rat 		lowest published toxic dose: 650 mg/kg/65 day- intermittent Vascular: BP lowering not characterized in autonomic section

Kidney, Ureter, and Bladder: Urine volume decreased or anuria

Kidney, Ureter, and Bladder: Other changes in urine composition 		JPETAB 294,948,2000
oral
rat 		lowest published toxic dose: 1,050 mg/kg/6 week- continuous Vascular: BP lowering not characterized in autonomic section JCPCDT 35,763,2000
oral
rat 		lowest published toxic dose: 1,750 mg/kg/10 week- continuous Vascular: Relaxation (isolated tissue) JCPCDT 35,763,2000
oral
rat 		lowest published toxic dose: 560 µg/kg/4 week- intermittent Vascular: BP lowering not characterized in autonomic section

Cardiac: Other changes 		CEXPB9 30,739,2003
oral
rat 		lowest published toxic dose: 150 mg/kg/15 day- continuous Vascular: BP lowering not characterized in autonomic section

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) 		JPETAB 307,1104,2003


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
International Agency for Research on Cancer (IARC) Cancer Review Human Inadequate Evidence IMEMDT 24,85,1980
International Agency for Research on Cancer (IARC) Cancer Review Group 3 IMSUDL 7,222,1987
TOXICOLOGY REVIEW
INTEAG 15,7,1974
TOXICOLOGY REVIEW
MUREAV 612,115,2006
TOXICOLOGY REVIEW
EJIME* 17,529,2006
TOXICOLOGY REVIEW
DIMON* 40,258,1994
TOXICOLOGY REVIEW
DIMON* 39,678,1993
TOXICOLOGY REVIEW
JAADDB 56,181,2007
TOXICOLOGY REVIEW
HUTOX* -,395,1996


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
N/R N/R N/R


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: X4187;
Number of Industries 1;
Total Number of Facilities 85;
Number of Occupations 3;
Total Number of Employees Exposed 8,409;
Total Number of Female Employees Exposed 7,509


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
N/R


REFERENCES:

CODEN
REFERENCE
AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920-
ANREAK Anatomical Record. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1906/08-
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894-
BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857-
CEXPB9 Clinical and Experimental Pharmacology and Physiology. (Blackwell Scientific Publications, (Australia) Pty Ltd., 107 Barry St., Carlton, Vic. 3053, Australia) V.1- 1974-
DIMON* Disease-a Month (Chicago : Year Book Publishers) V. 24- 1978-
EJIME* European Journal of Internal Medicine: The Official Journal of the European Federation of Internal Medicine (EFIM) (Elsevier) V.10- 1999-
EJPEDT European Journal of Pediatrics. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.121- 1975-
EXPADD Experimental Pathology (1981). (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.19- 1981-
FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939-
FCLPH* Fundamental & Clinical Pharmacology (Oxford : Blackwell Science) 2001-
HUTOX*
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972-
IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979-
INTEAG Internist. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1960-
JAADDB Journal of the American Academy of Dermatology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) 1979-
JAPMA8 Journal of the American Pharmaceutical Association, Scientific Edition. (Washington, DC) V.29-49, 1940-60. For publisher information, see JPMSAE.
JCPCDT Journal of Cardiovascular Pharmacology. (Raven Press, 1140 Ave. of the Americas, New York, NY 10036) V.1- 1979-
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
MDACAP Medicamentos de Actualidad. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1965-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928-
PCJOAU Pharmaceutical Chemistry Journal (English Translation). Translation of KHFZAN. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) No.1- 1967-
PLRCAT Pharmacological Research Communications. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1969-
PNASA6 Proceedings of the National Academy of Sciences of the United States of America. (National Academy of Sciences, Printing & Pub. Office, 2101 Constitution Ave., Washington, DC 20418) V.1- 1915-
RPTOAN Russian Pharmacology and Toxicology (English Translation). Translation of FATOAO. (Euromed Pub., 33, Woodlands Rd., Surbiton, Surrey, UK) V.30- 1967-
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-
TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973-

RTECS Compound Description:
   Tumorigen
   Drug
   Mutagen
   Reproductive Effector
   Human Data

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