*** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : QD1310000
CHEMICAL NAME           : Morphinan-6-alpha-ol,
                          7,8-didehydro-4,5-alpha-epoxy-3-methoxy-17-methyl-,
                          phosphate (1:1)
CAS REGISTRY NUMBER     : 52-28-8
LAST UPDATED            : 199710
DATA ITEMS CITED        : 34
MOLECULAR FORMULA       : C18-H21-N-O3.H3-O4-P
MOLECULAR WEIGHT        : 397.40
WISWESSER LINE NOTATION : T B6566 B6/CO 4ABBC R BX HO PN DU GHT&&TTJ FQ JO1 P1
                          &P-O4
COMPOUND DESCRIPTOR     : Drug
                          Mutagen
                          Reproductive Effector
                          Human
SYNONYMS/TRADE NAMES :
   * Codeine phosphate
   * (-)-Codeine phosphate
   * Morphinan-6-ol, 7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-,  
   (5-alpha,6-alpha)-, phosphate
   * Tricodein
 
                       *** HEALTH HAZARD DATA ***
 
                        ** ACUTE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - woman
DOSE/DURATION           : 3600 ug/kg/2D-I
TOXIC EFFECTS :
   Sense Organs and Special Senses (Eye) - miosis (pupillary constriction)
   Behavioral - sleep
   Vascular - BP lowering not characterized in autonomic section
REFERENCE :
   CPHADV Clinical Pharmacy.  (American Soc. of Hospital Pharmacists, 4630
   Montgomery Ave., Bethesda, MD 20814)  V.1-    1982- Volume(issue)/page/year:
   5,15,1986
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 5143 ug/kg/5D-I
TOXIC EFFECTS :
   Behavioral - sleep
   Vascular - BP lowering not characterized in autonomic section
REFERENCE :
   CPHADV Clinical Pharmacy.  (American Soc. of Hospital Pharmacists, 4630
   Montgomery Ave., Bethesda, MD 20814)  V.1-    1982- Volume(issue)/page/year:
   5,15,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 85 mg/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: #3163649
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 104 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
   Behavioral - convulsions or effect on seizure threshold
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: 133,117,1961
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 312 mg/kg
TOXIC EFFECTS :
   Behavioral - somnolence (general depressed activity)
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: 154,161,1966
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 54 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans
   Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium)  V.4-   
   1898-  Volume(issue)/page/year: 103,200,1955
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intramuscular
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 208 mg/kg
TOXIC EFFECTS :
   Behavioral - changes in motor activity (specific assay)
   Lungs, Thorax, or Respiration - dyspnea
   Gastrointestinal - hypermotility, diarrhea
REFERENCE :
   AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans
   Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium)  V.4-   
   1898-  Volume(issue)/page/year: 190,124,1971
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 237 mg/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: 128,384,1960
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 110 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: 19,1916,1969
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 80 mg/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: #3031377
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 62 mg/kg
TOXIC EFFECTS :
   Behavioral - convulsions or effect on seizure threshold
   Behavioral - ataxia
   Lungs, Thorax, or Respiration - other changes
REFERENCE :
   JJPAAZ Japanese Journal of Pharmacology.  (Japanese Pharmacological Soc.,
   c/o Dept. of Pharmacology, Faculty of Medicine, Kyoto Univ., Sakyo-ku, Kyoto
   606, Japan)  V.1-    1951-  Volume(issue)/page/year: 17,538,1967
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intramuscular
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 191 mg/kg
TOXIC EFFECTS :
   Behavioral - changes in motor activity (specific assay)
   Lungs, Thorax, or Respiration - dyspnea
   Gastrointestinal - hypermotility, diarrhea
REFERENCE :
   AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans
   Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium)  V.4-   
   1898-  Volume(issue)/page/year: 190,124,1971
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intracerebral
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 12 mg/kg
TOXIC EFFECTS :
   Behavioral - convulsions or effect on seizure threshold
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: 140,155,1963
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : 97800 ug/kg
TOXIC EFFECTS :
   Sense Organs and Special Senses (Eye) - lacrimation
   Behavioral - convulsions or effect on seizure threshold
   Gastrointestinal - nausea or vomiting
REFERENCE :
   OYYAA2 Oyo Yakuri.  Pharmacometrics.  (Oyo Yakuri Kenkyukai, CPO Box 180,
   Sendai 980-91, Japan) V.1-    1967-  Volume(issue)/page/year: 4,961,1970
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Mammal - cat
DOSE/DURATION           : 50 mg/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: #3031377
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rabbit
DOSE/DURATION           : 100 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   HBTXAC "Handbook of Toxicology," 4 vols., Philadelphia, W.B. Saunders Co.,
   1956-59  Volume(issue)/page/year: 1,72,1955
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rabbit
DOSE/DURATION           : 40 mg/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: #3031377
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - guinea pig
DOSE/DURATION           : 654 mg/kg
TOXIC EFFECTS :
   Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation)
   Lungs, Thorax, or Respiration - dyspnea
REFERENCE :
   OYYAA2 Oyo Yakuri.  Pharmacometrics.  (Oyo Yakuri Kenkyukai, CPO Box 180,
   Sendai 980-91, Japan) V.1-    1967-  Volume(issue)/page/year: 6,1207,1972
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - guinea pig
DOSE/DURATION           : 352 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: 27,1450,1977
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - guinea pig
DOSE/DURATION           : 140 mg/kg
TOXIC EFFECTS :
   Sense Organs and Special Senses (Eye) - lacrimation
REFERENCE :
   OYYAA2 Oyo Yakuri.  Pharmacometrics.  (Oyo Yakuri Kenkyukai, CPO Box 180,
   Sendai 980-91, Japan) V.1-    1967-  Volume(issue)/page/year: 6,1207,1972
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - guinea pig
DOSE/DURATION           : 117 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans
   Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium)  V.4-   
   1898-  Volume(issue)/page/year: 119,205,1959
 
TYPE OF TEST            : LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE       : Intraarterial
SPECIES OBSERVED        : Rodent - guinea pig
DOSE/DURATION           : 1 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und
   Pharmakologie.  (Berlin, Ger.) V.110-253, 1925-66.  For publisher
   information, see NSAPCC.  Volume(issue)/page/year: 131,171,1928
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Unreported
SPECIES OBSERVED        : Mammal - species unspecified
DOSE/DURATION           : 183 mg/kg
TOXIC EFFECTS :
   Lungs, Thorax, or Respiration - other changes
REFERENCE :
   CPBTAL Chemical and Pharmaceutical Bulletin.  (Japan Pub. Trading Co., USA,
   1255 Howard St., San Francisco, CA 94103)  V.6-    1958-
   Volume(issue)/page/year: 20,1699,1972
 
                 ** OTHER MULTIPLE DOSE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 4050 mg/kg/30D-I
TOXIC EFFECTS :
   Blood - changes in cell count (unspecified)
   Nutritional and Gross Metabolic - changes in sodium
   Related to Chronic Data - death
REFERENCE :
   KSRNAM Kiso to Rinsho.  Clinical Report.  (Yubunsha Co., Ltd., 1-5, Kanda
   Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan)  V.1-    1960-
   Volume(issue)/page/year: 5,1011,1971
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 2340 mg/kg/26W-I
TOXIC EFFECTS :
   Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
   Nutritional and Gross Metabolic - changes in potassium
   Biochemical - Enzyme inhibition, induction, or change in blood or tissue
   levels - phosphatases
REFERENCE :
   KSRNAM Kiso to Rinsho.  Clinical Report.  (Yubunsha Co., Ltd., 1-5, Kanda
   Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan)  V.1-    1960-
   Volume(issue)/page/year: 5,1011,1971
 
                          ** REPRODUCTIVE DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - mouse
DOSE                    : 110 mg/kg
SEX/DURATION            : female 9 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Specific Developmental Abnormalities - Central Nervous System
REFERENCE :
   DGDFA5 Development, Growth & Differentiation.  (Japan Pub. Trading Co.
   (USA), 1255 Howard St., San Francisco, CA 94103)  V.11-    1969-
   Volume(issue)/page/year: 22,61,1980
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - hamster
DOSE                    : 97 mg/kg
SEX/DURATION            : female 8 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Specific Developmental Abnormalities - Central Nervous System
REFERENCE :
   AJOGAH American Journal of Obstetrics and Gynecology.  (C.V. Mosby Co.,
   11830 Westline Industrial Dr., St. Louis, MO 63146)  V.1-    1920-
   Volume(issue)/page/year: 123,705,1975

                              *** REVIEWS ***
 
   TOXICOLOGY REVIEW
   DPIRDU Dangerous Properties of Industrial Materials Report.  (Van Nostrand
   Reinhold, 115 Fifth Ave., New York, NY 10003)  V.1-    1981-
   Volume(issue)/page/year: 3(2),14,1983

         *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA ***

NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA :
   NOHS - National Occupational Hazard Survey (1974)
     NOHS Hazard Code - 84592
       No. of Facilities: 1110 (estimated)
       No. of Industries: 3
       No. of Occupations: 8
       No. of Employees: 4561 (estimated)
   
   NOES - National Occupational Exposure Survey (1983)
     NOES Hazard Code - 84592
       No. of Facilities: 500 (estimated)
       No. of Industries: 2
       No. of Occupations: 9
       No. of Employees: 30682 (estimated)
       No. of Female Employees: 28092 (estimated)

                          *** STATUS IN U.S. ***
 
   EPA GENETOX PROGRAM 1988, Negative: Sperm morphology-mouse
   
   EPA GENETOX PROGRAM 1988, Inconclusive: Mammalian micronucleus
   
   EPA TSCA Section 8(d) unpublished health/safety studies
   
   EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JUNE 1998

 
                            *** END OF RECORD ***