*** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : XI0330600
CHEMICAL NAME           : 5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic
                          acid, 7-(((4-(2-amino-1-carboxy-
                          2-oxoethyl)-1,3-dithietan-2-yl)carbonyl)amino)-7-meth
                          oxy-3-(((1-methyl-1H- tetrazol-5-yl)
                          thio)methyl)-8-oxo-, disodium salt, (6R-cis)-
CAS REGISTRY NUMBER     : 74356-00-6
LAST UPDATED            : 199806
DATA ITEMS CITED        : 19
MOLECULAR FORMULA       : C17-H15-N7-O8-S4.2Na
MOLECULAR WEIGHT        : 619.61
COMPOUND DESCRIPTOR     : Drug
                          Reproductive Effector
                          Human
SYNONYMS/TRADE NAMES :
   * Apatef
   * Cefotetan disodium salt
   * Cefotetan sodium
   * Ceftenon
   * Cepan
   * Darvilen
   * ICI 156834 disodium
   * Yamatetan
   * YM 09330
 
                       *** HEALTH HAZARD DATA ***
 
                        ** ACUTE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 800 mg/kg/4W-I
TOXIC EFFECTS :
   Lungs, Thorax, or Respiration - other changes
REFERENCE :
   AIMEAS Annals of Internal Medicine.  (American College of Physicians, 4200
   Pine St., Philadelphia, PA 19104)  V.1-    1927-  Volume(issue)/page/year:
   116,522,1992
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 814 mg/kg/18D-C
TOXIC EFFECTS :
   Kidney, Ureter, Bladder - interstitial nephritis
   Skin and Appendages - dermatitis, allergic (after systemic exposure)
   Nutritional and Gross Metabolic - body temperature increase
REFERENCE :
   AJKDDP American Journal of Kidney Diseases.  (Grune & Stratton, Inc.,
   Journal Subscription Dept., POB 6280, Duluth, MN 55806)  V.1-    1981-
   Volume(issue)/page/year: 16,259,1990
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : >10 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,565,1990
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 8250 mg/kg
TOXIC EFFECTS :
   Sense Organs and Special Senses (Eye) - ptosis
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - changes in motor activity (specific assay)
REFERENCE :
   NKRZAZ Chemotherapy (Tokyo).  (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki,
   Shinagawa-Ku, Tokyo 141, Japan)  V.1-    1953- Volume(issue)/page/year:
   30(Suppl 1),208,1982
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : >10 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,565,1990
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 6790 mg/kg
TOXIC EFFECTS :
   Behavioral - tremor
   Behavioral - convulsions or effect on seizure threshold
   Lungs, Thorax, or Respiration - acute pulmonary edema
REFERENCE :
   NKRZAZ Chemotherapy (Tokyo).  (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki,
   Shinagawa-Ku, Tokyo 141, Japan)  V.1-    1953- Volume(issue)/page/year:
   30(Suppl 1),208,1982
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : >10 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,565,1990
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 8120 mg/kg
TOXIC EFFECTS :
   Sense Organs and Special Senses (Eye) - ptosis
   Behavioral - altered sleep time (including change in righting reflex)
   Behavioral - changes in motor activity (specific assay)
REFERENCE :
   NKRZAZ Chemotherapy (Tokyo).  (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki,
   Shinagawa-Ku, Tokyo 141, Japan)  V.1-    1953- Volume(issue)/page/year:
   30(Suppl 1),208,1982
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : >10 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,565,1990
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 4990 mg/kg
TOXIC EFFECTS :
   Behavioral - tremor
   Behavioral - convulsions or effect on seizure threshold
   Lungs, Thorax, or Respiration - acute pulmonary edema
REFERENCE :
   NKRZAZ Chemotherapy (Tokyo).  (Nippon Kagaku Ryoho Gakkai, 2-20-8 Kamiosaki,
   Shinagawa-Ku, Tokyo 141, Japan)  V.1-    1953- Volume(issue)/page/year:
   30(Suppl 1),208,1982
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : >6 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,661,1995
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Mammal - dog
DOSE/DURATION           : >6 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,565,1990
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Primate - monkey
DOSE/DURATION           : >6 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,661,1995
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rabbit
DOSE/DURATION           : >6 gm/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   NIIRDN Drugs in Japan (Ethical Drugs).  (Yakugyo Jiho Co., Ltd., Tokyo,
   Japan)  Volume(issue)/page/year: -,565,1990
 
                 ** OTHER MULTIPLE DOSE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 182 gm/kg/26W-C
TOXIC EFFECTS :
   Liver - changes in liver weight
   Kidney, Ureter, Bladder - urine volume decreased
   Kidney, Ureter, Bladder - changes in bladder weight
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: 16,98,1982
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 35 gm/kg/5W-I
TOXIC EFFECTS :
   Gastrointestinal - nausea or vomiting
   Liver - changes in liver weight
   Endocrine - changes in spleen weight
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: 16,15,1982
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 91 gm/kg/13W-I
TOXIC EFFECTS :
   Gastrointestinal - hypermotility, diarrhea
   Gastrointestinal - nausea or vomiting
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: 16,69,1982
 
                          ** REPRODUCTIVE DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 5460 mg/kg
SEX/DURATION            : male 26 week(s) pre-mating
TOXIC EFFECTS :
   Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland,
   accessory glands
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: 16,98,1982
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Intravenous
SPECIES OBSERVED        : Rodent - rat
DOSE                    : 2700 mg/kg
SEX/DURATION            : female 17-22 day(s) after conception
                          lactating female 21 day(s) post-birth
TOXIC EFFECTS :
   Reproductive - Maternal Effects - parturition
   Reproductive - Effects on Newborn - behavioral
   Reproductive - Effects on Newborn - physical
REFERENCE :
   OYYAA2 Oyo Yakuri.  Pharmacometrics.  (Oyo Yakuri Kenkyukai, CPO Box 180,
   Sendai 980-91, Japan) V.1-    1967-  Volume(issue)/page/year: 23,767,1982
 
                            *** END OF RECORD ***