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3 - Biphenylcarboxylic acid, 2',4' - difluoro - 4 - hydroxy -

RTECS #: DV2030000

CAS #: 22494-42-4

UPDATE: February 2009 MW: 250.21 MF: C13H8F2O3


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. MUTATION DATA:
  3. REPRODUCTIVE EFFECTS DATA:
  4. ACUTE TOXICITY DATA:
  5. OTHER MULTIPLE DOSE DATA:
  6. REVIEWS:
  7. NIOSH DOCUMENTATION AND SURVEILLANCE:
  8. REFERENCES:

SYNONYMS:

  1. (1,1' - Biphenyl) - 3 - carboxylic acid, 2',4' - difluoro - 4 - hydroxy -
  2. 2',4' - Difluoro - 4 - hydroxy - 3 - biphenylcarboxylic acid
  3. 2',4' - Difluoro - 4 - hydroxy - (1,1' - biphenyl) - 3 - carboxylic acid
  4. 2 - (Hydroxy) - 5 - (2,4 - difluorophenyl) benzoic acid
  5. 5 - (2,4 - Difluorophenyl) salicylic acid
  6. Diflunisal
  1. Dolobid
  2. Dolobil
  3. Dolobis
  4. Flovacil
  5. Fluniget
  6. MK 647


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
N/R
 N/R N/R N/R


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
cytogenetic analysis intraperitoneal
mouse 		100 mg/kg MUREAV 370,1,1996
cytogenetic analysis oral
mouse 		350 mg/kg MUREAV 370,1,1996
sister chromatid exchange intraperitoneal
mouse 		50 mg/kg MUREAV 370,1,1996
sister chromatid exchange oral
mouse 		350 mg/kg MUREAV 370,1,1996


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
rat 		lowest published toxic dose: 500 mg/kg (9-10 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system 		BDERB* 68,47,2003
oral
rabbit 		lowest published toxic dose: 520 mg/kg (6-18 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		TJADAB 30,319,1984
oral
rabbit 		lowest published toxic dose: 780 mg/kg (6-18 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) TJADAB 30,319,1984
oral
rabbit 		lowest published toxic dose: 750 mg/kg (9-11 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Eye, ear 		BDERB* 68,47,2003
oral
rabbit 		lowest published toxic dose: 750 mg/kg (9-11 day pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system BDERB* 68,47,2003


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
N/R
 N/R N/R N/R


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lethal dose (50 percent kill): 124 mg/kg N/R IYKEDH 15,688,1984
intraperitoneal
rat 		lethal dose (50 percent kill): 159 mg/kg N/R IYKEDH 15,688,1984
intravenous
rat 		lowest published toxic dose: 500 mg/kg Liver: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		BCPCA6 67,2141,2004
oral
human 		lowest published toxic dose: 71 mg/kg/5 day- intermittent Behavioral: Tolerance

Liver: Jaundice, cholestatic 		BMJOAE 2,736,1978
oral
man 		lowest published toxic dose: 429 mg/kg/17 week- intermittent Blood: Angranulocytosis

Nutritional and Gross Metabolic: Body temperature increase 		ANZJB8 16,811,1986
oral
mouse 		lethal dose (50 percent kill): 439 mg/kg Behavioral: Tremor

Behavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression 		BCPHBM 4,19S,1977
oral
rat 		lethal dose (50 percent kill): 392 mg/kg N/R IYKEDH 15,688,1984
oral
rabbit 		lethal dose (50 percent kill): 603 mg/kg Behavioral: Tremor

Behavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression 		BCPHBM 4,19S,1977
subcutaneous
mouse 		lethal dose (50 percent kill): 212 mg/kg N/R NIIRDN -,555,1995
subcutaneous
rat 		lethal dose (50 percent kill): 185 mg/kg N/R IYKEDH 15,688,1984


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
rat 		lowest published toxic dose: 800 mg/kg/4 day- intermittent Gastrointestinal: Ulceration or bleeding from stomach

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		TXAPA9 52,454,1980
oral
rat 		lowest published toxic dose: 9,400 mg/kg/14 week- intermittent Gastrointestinal: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		BCPHBM 4,19S,1977


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
TOXICOLOGY REVIEW
MUREAV 488,151,2001
TOXICOLOGY REVIEW
EMMUEG 43,143,2004
TOXICOLOGY REVIEW
APHRER 38,1159,2004
TOXICOLOGY REVIEW
EJIME* 17,529,2006
TOXICOLOGY REVIEW
DIMON* 39,678,1993
TOXICOLOGY REVIEW
TOPADD 32(Suppl. 2),71,2004
TOXICOLOGY REVIEW
FCLPH* 17,393,2003
TOXICOLOGY REVIEW
PHREP* 59,247,2007


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
N/R N/R N/R


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: X6814;
Number of Industries 1;
Total Number of Facilities 16;
Number of Occupations 1;
Total Number of Employees Exposed 94;
Total Number of Female Employees Exposed 62


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
N/R


REFERENCES:

CODEN
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-
APHRER Annals of Pharmacotherpy. (Harvey Whitney Books Co., POB 42696, Cincinnati, OH 45242) V. 26- 1992-
BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958-
BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1974-
BDERB*
BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857-
DIMON* Disease-a Month (Chicago : Year Book Publishers) V. 24- 1978-
EJIME* European Journal of Internal Medicine: The Official Journal of the European Federation of Internal Medicine (EFIM) (Elsevier) V.10- 1999-
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
FCLPH* Fundamental & Clinical Pharmacology (Oxford : Blackwell Science) 2001-
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan)
PHREP*
TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
TOPADD Toxicologic Pathology. (c/o Dr. F.A. de la Iglesia, Warner-Lambert Co., Pharmaceutical Research Div., POB 1047, Ann Arbor, MI 48106) V.6(3/4)- 1978-
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-

Used as an analgesic and anti-inflammatory agent

FDA-proprietary drug

RTECS Compound Description:
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   Mutagen
   Reproductive Effector
   Human Data

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