*** 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 ***