*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : TJ2100000 CHEMICAL NAME : Physostigmine CAS REGISTRY NUMBER : 57-47-6 LAST UPDATED : 199710 DATA ITEMS CITED : 27 MOLECULAR FORMULA : C15-H21-N3-O2 MOLECULAR WEIGHT : 275.39 WISWESSER LINE NOTATION : T B556 EN GNTT&J B1 E1 G1 KOVM1 COMPOUND DESCRIPTOR : Drug Reproductive Effector Human Natural Product SYNONYMS/TRADE NAMES : * Carbamic acid, methyl-, ester with eseroline * CS 58525 * Eserine * Eserolein, methylcarbamate (ester) * Fysostigmin * MCV 4484 * NIH 10421 * (-)-Physostigmine * Physostol *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 20 mg/kg TOXIC EFFECTS : Behavioral - coma Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - nausea or vomiting REFERENCE : 34ZIAG "Toxicology of Drugs and Chemicals," Deichmann, W.B., New York, Academic Press, Inc., 1969 Volume(issue)/page/year: -,475,1969 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 40 ug/kg/5D-I TOXIC EFFECTS : Vascular - BP elevation not characterized in autonomic section REFERENCE : AJPSAO American Journal of Psychiatry. (American Psychiatric Assoc., Circulation Dept., 1400 K St., NW, Washington, DC 20005) V.78- 1921- Volume(issue)/page/year: 143,910,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 3920 ug/kg/2W-I TOXIC EFFECTS : Behavioral - muscle contraction or spasticity REFERENCE : NEURAI Neurology. (Modern Medicine Pub., Inc., 1 E. First St., Duluth, MN 55802) V.1- 1951- Volume(issue)/page/year: 37,345,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 12 mg/kg/60D-I TOXIC EFFECTS : Behavioral - muscle contraction or spasticity REFERENCE : NEURAI Neurology. (Modern Medicine Pub., Inc., 1 E. First St., Duluth, MN 55802) V.1- 1951- Volume(issue)/page/year: 37,345,1987 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - man DOSE/DURATION : 882 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 85DCAI "Poisoning; Toxicology, Symptoms, Treatments," 2nd ed., Arena, J.M., Springfield, IL, C.C. Thomas, 1970 Volume(issue)/page/year: 2,73,1970 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 22,1926,1972 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 3 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 85IXA4 "Structure et Activite Pharmacodyanmique des Medicaments du Systeme Nerveux Vegetatif," Bovet, D., and F. Bovet-Nitti, New York, S. Karger, 1948 Volume(issue)/page/year: -,452,1948 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 644 ug/kg TOXIC EFFECTS : Behavioral - muscle contraction or spasticity Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - cyanosis REFERENCE : FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939- Volume(issue)/page/year: 43,717,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 740 ug/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - muscle weakness REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 123,121,1958 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 400 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 58,337,1936 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 330 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 33,577,1990 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Parenteral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 600 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #5306825 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 1138 ug/kg TOXIC EFFECTS : Behavioral - muscle contraction or spasticity Gastrointestinal - changes in structure or function of salivary glands Gastrointestinal - ulceration or bleeding from large intestine REFERENCE : FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. (Bethesda, MD) V.1-46, 1942-87. Volume(issue)/page/year: 5,184,1946 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - cat DOSE/DURATION : 660 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 88,39,1946 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 11200 ug/kg TOXIC EFFECTS : Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase REFERENCE : DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78- Volume(issue)/page/year: 3,319,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 2470 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ABMHAM Archives Belges de Medecine Sociale, Hygiene, Medecine du Trevail et Medecine Legale. (Quartier Esplanade no.6, 1010 Brussels, Belgium) V.4- 1946- Volume(issue)/page/year: (Suppl),226,1984 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 3 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 85IXA4 "Structure et Activite Pharmacodyanmique des Medicaments du Systeme Nerveux Vegetatif," Bovet, D., and F. Bovet-Nitti, New York, S. Karger, 1948 Volume(issue)/page/year: -,452,1948 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 500 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 85IXA4 "Structure et Activite Pharmacodyanmique des Medicaments du Systeme Nerveux Vegetatif," Bovet, D., and F. Bovet-Nitti, New York, S. Karger, 1948 Volume(issue)/page/year: -,452,1948 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 2200 ug/kg TOXIC EFFECTS : Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - true cholinesterase REFERENCE : DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78- Volume(issue)/page/year: 3,319,1980 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Bird - pigeon DOSE/DURATION : 450 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : HBAMAK "Abdernalden's Handbuch der Biologischen Arbeitsmethoden." (Leipzig, Ger. Dem. Rep.) Volume(issue)/page/year: 4,1289,1935 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Mammal - species unspecified DOSE/DURATION : 600 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #5409948 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE : 333 ug/kg SEX/DURATION : male 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles) REFERENCE : ANENAG Annales d'Endocrinologie. (Masson Editeur, 120 Blvd. Saint-Germain, F-25280 Paris Cedex 06, France) V.1- 1939- Volume(issue)/page/year: 24(Suppl 3),1,1963 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE : 50 ug/kg SEX/DURATION : female 13 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - biochemical and metabolic Reproductive - Effects on Newborn - behavioral REFERENCE : FEPRA7 Federation Proceedings, Federation of American Societies for Experimental Biology. (Bethesda, MD) V.1-46, 1942-87. Volume(issue)/page/year: 31,596,1972 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4159 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 103 (estimated) No. of Female Employees: 52 (estimated) *** STATUS IN U.S. *** EPA TSCA Section 8(b) CHEMICAL INVENTORY EPA TSCA Section 8(d) unpublished health/safety studies EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JUNE 1998 *** END OF RECORD ***