*** 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 ***