*** CHEMICAL IDENTIFICATION ***

RTECS NUMBER            : DV2030000
CHEMICAL NAME           : 3-Biphenylcarboxylic acid, 2',4'-difluoro-4-hydroxy-
CAS REGISTRY NUMBER     : 22494-42-4
BEILSTEIN REFERENCE NO. : 2654431
LAST UPDATED            : 199806
DATA ITEMS CITED        : 18
MOLECULAR FORMULA       : C13-H8-F2-O3
MOLECULAR WEIGHT        : 250.21
WISWESSER LINE NOTATION : QVR BQ ER BF DF
COMPOUND DESCRIPTOR     : Drug
                          Mutagen
                          Reproductive Effector
                          Human
SYNONYMS/TRADE NAMES :
   * (1,1'-Biphenyl)-3-carboxylic acid, 2',4'-difluoro-4-hydroxy-
   * Diflunisal
   * 2',4'-Difluoro-4-hydroxy-(1,1'-biphenyl)-3-carboxylic acid
   * 2',4'-Difluoro-4-hydroxy-3-biphenylcarboxylic acid
   * 5-(2,4-Difluorophenyl)salicylic acid
   * Dolobid
   * Dolobil
   * Dolobis
   * Flovacil
   * Fluniget
   * 2-(Hydroxy)-5-(2,4-difluorophenyl)benzoic acid
   * MK 647
 
                       *** HEALTH HAZARD DATA ***
 
                        ** ACUTE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human
DOSE/DURATION           : 71 mg/kg/5D-I
TOXIC EFFECTS :
   Behavioral - tolerance
   Liver - jaundice, cholestatic
REFERENCE :
   BMJOAE British Medical Journal.  (British Medical Assoc., BMA House,
   Tavistock Sq., London WC1H 9JR, UK)  V.1-    1857- Volume(issue)/page/year:
   2,736,1978
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Human - man
DOSE/DURATION           : 429 mg/kg/17W-I
TOXIC EFFECTS :
   Blood - agranulocytosis
   Nutritional and Gross Metabolic - body temperature increase
REFERENCE :
   ANZJB8 Australian and New Zealand Journal of Medicine.  (Modern Medicine of
   Australia Pty., Ltd., 100 Pacific Highway, North Sydney, 2060, Australia)
   V.1-    1971-  Volume(issue)/page/year: 16,811,1986
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 392 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   IYKEDH Iyakuhin Kenkyu.  Study of Medical Supplies.  (Nippon Koteisho
   Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan)  V.1- 1970- 
   Volume(issue)/page/year: 15,688,1984
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 159 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   IYKEDH Iyakuhin Kenkyu.  Study of Medical Supplies.  (Nippon Koteisho
   Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan)  V.1- 1970- 
   Volume(issue)/page/year: 15,688,1984
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 185 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   IYKEDH Iyakuhin Kenkyu.  Study of Medical Supplies.  (Nippon Koteisho
   Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan)  V.1- 1970- 
   Volume(issue)/page/year: 15,688,1984
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 439 mg/kg
TOXIC EFFECTS :
   Behavioral - tremor
   Behavioral - ataxia
   Lungs, Thorax, or Respiration - respiratory depression
REFERENCE :
   BCPHBM British Journal of Clinical Pharmacology.  (Blackwell Scientific Pub.
   Ltd., POB 88, Oxford, UK)  V.1-    1974-  Volume(issue)/page/year:
   4,19S,1977
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Intraperitoneal
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 124 mg/kg
TOXIC EFFECTS :
   Details of toxic effects not reported other than lethal dose value
REFERENCE :
   IYKEDH Iyakuhin Kenkyu.  Study of Medical Supplies.  (Nippon Koteisho
   Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan)  V.1- 1970- 
   Volume(issue)/page/year: 15,688,1984
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Subcutaneous
SPECIES OBSERVED        : Rodent - mouse
DOSE/DURATION           : 212 mg/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: -,555,1995
 
TYPE OF TEST            : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rabbit
DOSE/DURATION           : 603 mg/kg
TOXIC EFFECTS :
   Behavioral - tremor
   Behavioral - ataxia
   Lungs, Thorax, or Respiration - respiratory depression
REFERENCE :
   BCPHBM British Journal of Clinical Pharmacology.  (Blackwell Scientific Pub.
   Ltd., POB 88, Oxford, UK)  V.1-    1974-  Volume(issue)/page/year:
   4,19S,1977
 
                 ** OTHER MULTIPLE DOSE TOXICITY DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 800 mg/kg/4D-I
TOXIC EFFECTS :
   Gastrointestinal - ulceration or bleeding from stomach
   Related to Chronic Data - death
REFERENCE :
   TXAPA9 Toxicology and Applied Pharmacology.  (Academic Press, Inc., 1 E.
   First St., Duluth, MN 55802) V.1-    1959-  Volume(issue)/page/year:
   52,454,1980
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rat
DOSE/DURATION           : 9400 mg/kg/14W-I
TOXIC EFFECTS :
   Gastrointestinal - other changes
   Related to Chronic Data - death
REFERENCE :
   BCPHBM British Journal of Clinical Pharmacology.  (Blackwell Scientific Pub.
   Ltd., POB 88, Oxford, UK)  V.1-    1974-  Volume(issue)/page/year:
   4,19S,1977
 
                          ** REPRODUCTIVE DATA **
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rabbit
DOSE                    : 520 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)
   Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
   TJADAB Teratology, The International Journal of Abnormal Development. (Alan
   R. Liss, Inc., 41 E. 11th St., New York, NY 10003)  V.1-    1968-
   Volume(issue)/page/year: 30,319,1984
 
TYPE OF TEST            : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE       : Oral
SPECIES OBSERVED        : Rodent - rabbit
DOSE                    : 780 mg/kg
SEX/DURATION            : female 6-18 day(s) after conception
TOXIC EFFECTS :
   Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
   resorbed implants per total number of implants)
REFERENCE :
   TJADAB Teratology, The International Journal of Abnormal Development. (Alan
   R. Liss, Inc., 41 E. 11th St., New York, NY 10003)  V.1-    1968-
   Volume(issue)/page/year: 30,319,1984
 
                            ** MUTATION DATA **
 
TYPE OF TEST            : Cytogenetic analysis
ROUTE OF EXPOSURE       : Intraperitoneal
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 100 mg/kg
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 370,1,1996
 
TYPE OF TEST            : Cytogenetic analysis
ROUTE OF EXPOSURE       : Oral
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 350 mg/kg
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 370,1,1996
 
TYPE OF TEST            : Sister chromatid exchange
ROUTE OF EXPOSURE       : Intraperitoneal
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 50 mg/kg
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 370,1,1996
 
TYPE OF TEST            : Sister chromatid exchange
ROUTE OF EXPOSURE       : Oral
TEST SYSTEM             : Rodent - mouse
DOSE/DURATION           : 350 mg/kg
REFERENCE :
   MUREAV Mutation Research.  (Elsevier Science Pub. B.V., POB 211, 1000 AE
   Amsterdam, Netherlands) V.1-    1964-  Volume(issue)/page/year: 370,1,1996

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

NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA :
   NOES - National Occupational Exposure Survey (1983)
     NOES Hazard Code - X6814
       No. of Facilities: 16 (estimated)
       No. of Industries: 1
       No. of Occupations: 1
       No. of Employees: 94 (estimated)
       No. of Female Employees: 62 (estimated)

 
                            *** END OF RECORD ***