*** 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 ***