*** CHEMICAL IDENTIFICATION *** RTECS NUMBER : DL0705000 CHEMICAL NAME : 2H-1,2-Benzothiazine-3-carboxamide, 4-hydroxy-2-methyl-N-2-pyridinyl-, 1,1-dioxide CAS REGISTRY NUMBER : 36322-90-4 BEILSTEIN REFERENCE NO. : 0627692 LAST UPDATED : 199801 DATA ITEMS CITED : 29 MOLECULAR FORMULA : C15-H13-N3-O4-S MOLECULAR WEIGHT : 331.37 WISWESSER LINE NOTATION : T66 BSWNJ C1 EQ DVM- BT6NJ COMPOUND DESCRIPTOR : Drug Reproductive Effector Human SYNONYMS/TRADE NAMES : * BAXO * CHF 1251 * CP 16171 * Feldene * 4-Hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazin-3-caboxyamid-1,1-di oxid * 4-Hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide-1,1- dioxide * Piroftal * Piroxicam * Pyroxycam * Roxicam *** HEALTH HAZARD DATA *** ** ACUTE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 7636 mg/kg/6W-I TOXIC EFFECTS : Kidney, Ureter, Bladder - interstitial nephritis REFERENCE : AJNED9 American Journal of Nephrology. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.1- 1981- Volume(issue)/page/year: 5,142,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - child DOSE/DURATION : 7143 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Blood - aplastic anemia Nutritional and Gross Metabolic - other changes REFERENCE : SAMJAF South African Medical Journal. (Medical Assoc. of South Africa, Secy., P.O. Box 643, Cape Town, S. Africa) V.6- 1932- Volume(issue)/page/year: 66,31,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 52 mg/kg/26W-I TOXIC EFFECTS : Nutritional and Gross Metabolic - metabolic acidosis REFERENCE : AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 99,282,1983 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 1200 ug/kg/3D-I TOXIC EFFECTS : Skin and Appendages - dermatitis, other (after systemic exposure) REFERENCE : JRHUA9 Journal of Rheumatology. (920 Yonge St., Suite 608, Toronto, Ont., Canada) V.1- 1974- Volume(issue)/page/year: 11,554,1984 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - man DOSE/DURATION : 3714 mg/kg/13D-I TOXIC EFFECTS : Blood - agranulocytosis Skin and Appendages - dermatitis, allergic (after systemic exposure) REFERENCE : NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 309,795,1983 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 2400 ug/kg TOXIC EFFECTS : Liver - hepatitis, fibrous (cirrhosis, post-necrotic scarring) Liver - jaundice, other or unclassified Kidney, Ureter, Bladder - other changes in urine composition REFERENCE : BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 293,540,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human - woman DOSE/DURATION : 28 mg/kg TOXIC EFFECTS : Behavioral - headache Gastrointestinal - ulceration or bleeding from duodenum Gastrointestinal - nausea or vomiting REFERENCE : AMSVAZ Acta Medica Scandinavica. (Almqvist & Wiksell, POB 45150, S-10430 Stockholm, Sweden) V.52-224, 1919-88. Volume(issue)/page/year: 216,335,1984 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 216 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: 28,1714,1978 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Administration onto the skin SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >5 gm/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 37(11),-,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 335 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4639,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 148 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4639,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Rectal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 400 mg/kg TOXIC EFFECTS : Behavioral - analgesia Biochemical - Metabolism (Intermediary) - effect on inflammation or mediation of inflammation REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,87,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 250 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #0079639 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 290 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : RPTOAN Russian Pharmacology and Toxicology (English Translation). Translation of FATOAO. (Euromed Pub., 33, Woodlands Rd., Surbiton, Surrey, UK) V.30- 1967- Volume(issue)/page/year: 49,98,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 300 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4639,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 108 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4639,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 1 gm/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4639,1980 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 388 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ATSUDG Archives of Toxicology, Supplement. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) No.1- 1978- Volume(issue)/page/year: 7,365,1984 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - hamster DOSE/DURATION : 170 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : ATSUDG Archives of Toxicology, Supplement. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) No.1- 1978- Volume(issue)/page/year: 7,365,1984 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 600 mg/kg/30D-I TOXIC EFFECTS : Gastrointestinal - ulceration or bleeding from small intestine Blood - normocytic anemia REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 35(1),-,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1825 mg/kg/1Y-I TOXIC EFFECTS : Gastrointestinal - ulceration or bleeding from stomach Kidney, Ureter, Bladder - other changes Blood - normocytic anemia REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 35(1),-,1984 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 35 mg/kg SEX/DURATION : female 15-21 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - parturition REFERENCE : TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 30,59,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 110 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - parturition Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4655,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 110 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4655,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 110 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4655,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 55 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - live birth index (measured after birth) REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4655,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE : 34 mg/kg SEX/DURATION : female 1-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) REFERENCE : TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 30,59,1984 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE : 260 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4655,1980 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rabbit DOSE : 910 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 8,4655,1980 *** END OF RECORD ***