CAS 637-07-0|clofibrate
| Common Name | clofibrate | ||
|---|---|---|---|
| CAS Number | 637-07-0 | Molecular Weight | 242.699 |
| Density | 1.1±0.1 g/cm3 | Boiling Point | 274.8±0.0 °C at 760 mmHg |
| Molecular Formula | C12H15ClO3 | Melting Point | / |
| MSDS | ChineseUSA | Flash Point | 115.1±19.9 °C |
| Symbol | GHS05, GHS07 | Signal Word | Danger |
Names
| Name | clofibrate |
|---|---|
| Synonym | More Synonyms |
clofibrate BiologicalActivity
| Description | Clofibrate is an agonist of PPAR, with EC50s of 50 μM, ∼500 μM for murine PPARα and PPARγ, and 55 μM, ∼500 μM for human PPARα and PPARγ, respectively. |
|---|---|
| Related Catalog | Research Areas >>Metabolic Disease |
| Target | PPARα:50 μM (EC50) PPARγ:500 μM (EC50) |
| In Vitro | Clofibrate is a PPAR agonist, with E50s of 50 μM, ∼500 μM for murine PPARα and PPARγ, and 55 μM, ∼500 μM for human PPARα and PPARγ, respectively[1]. Clofibrate (0.5, 1, 2 mM) increases FABP1 expression in two fatty acid (FA)-treated rat hepatoma cells. Clofibrate lowers ROS levels after early treatment, much more than late treatment in FA-treated cells[2]. |
| In Vivo | Clofibrate (0.5%) up-regulates serum concentrations and hepatic expression of FGF21 in fetuses, with a return to basal levels after Clofibrate administration withdrawal. Clofibrate administration-offspring have significantly higher expression of thermogenic genes (Ucp1, Cidea, Ppara Ppargc1a, Cpt1b) and UCP1 protein levels in response to HFD in inguinal fat, but not in retroperitoneal (combined with perirenal) or epididymal fat[3]. |
| Cell Assay | Cells are seeded at a density of 2.5 × 104 cells/well (for WST-1, intracellular lipid droplet quantification and dichlorofluorescein (DCF) assay, 96-well plates) and 1 × 105 cells/well (for Nile Red Staining, 12-well plates) in MEM/EBSS medium and incubated overnight for adherence. The next day cell culture medium is replaced with freshly prepared medium containing the fatty acid mixture oleate:palmitate (2:1) in presence of 3% fatty-acid-free bovine serum albumin. Cells are treated with 0, 0.5, 1, 2, and 3 mM fatty acid (FA) mixture for 24 and 48 hr at 37°C in a humidified incubator in an atmosphere of 95% air and 5% CO2. Clofibrate is used to increase levels of FABP1 in treated cell cultures. Clofibrate (500 μM) is dissolved in DMSOand later added to the medium (DMSO < 0.1% v/v in final volume). Control cells are incubated with DMSO alone. Four different cell treatments includ 1-day FA treatment, 2-day FA treatment, early clofibrate intervention and late clofibrate intervention[1]. |
| Animal Admin | Female and male C57BL/6JNarl mice are used for breeding. Females with parity from 1 to 5 are used. Pregnant females are fed either a control (C) or experimental (CF) diet from breeding to parturition. The C diet is based on an AIN-93M diet with a slight modification to contain 21 kcal% fat from soybean oil, whereas the CF diet is the C diet with addition of 0.5% clofibrate. Pregnancy is dated by the presence of a vaginal plug (defined as pregnancy day 1). After spontaneous parturition (pregnancy day 19.5 ± 0.5), all littermates are uniformly nursed by dams fed the C diet for 3 wk, with litter sizes adjusted to 8-10, weaned onto a nonpurified standard diet for 4 wk, and then switched to a HFD (51 kcal% fat, butter-based) for 5 wk. In this study, only male offspring are used and 2 groups of offspring are designated, according to their mother's diet (C or CF). All mice are kept in a room maintained at 23 ± 2°C, with a controlled 12-h-light:-dark cycle with ad libitum to feed and drinking water. Body weight and feed intake are recorded weekly[3]. |
| References | [1]. Willson TM, et al. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000 Feb 24;43(4):527-50. [2]. Chen Y, et al. Clofibrate Attenuates ROS Production by Lipid Overload in Cultured Rat Hepatoma Cells. J Pharm Pharm Sci. 2017;20(0):239-251. [3]. Chen SH, et al. Prenatal PPARα activation by clofibrate increases subcutaneous fat browning in male C57BL/6J mice fed a high-fat diet during adulthood. PLoS One. 2017 Nov 2;12(11):e0187507. |
Chemical & Physical Properties
| Density | 1.1±0.1 g/cm3 |
|---|---|
| Boiling Point | 274.8±0.0 °C at 760 mmHg |
| Molecular Formula | C12H15ClO3 |
| Molecular Weight | 242.699 |
| Flash Point | 115.1±19.9 °C |
| Exact Mass | 242.070969 |
| PSA | 35.53000 |
| LogP | 3.32 |
| Vapour Pressure | 0.0±0.5 mmHg at 25°C |
| Index of Refraction | 1.505 |
| InChIKey | KNHUKKLJHYUCFP-UHFFFAOYSA-N |
| SMILES | CCOC(=O)C(C)(C)Oc1ccc(Cl)cc1 |
Toxicological Information
CHEMICAL IDENTIFICATION |
ACUTE TOXICITY DATA - TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Human - man
- DOSE/DURATION :
- 4232 mg/kg/57W-I
- TOXIC EFFECTS :
- Behavioral - muscle weakness Behavioral - muscle contraction or spasticity Musculoskeletal - other changes
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Human - man
- DOSE/DURATION :
- 1071 ug/kg
- TOXIC EFFECTS :
- Behavioral - tremor
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Human - woman
- DOSE/DURATION :
- 80 mg/kg/2D-I
- TOXIC EFFECTS :
- Nutritional and Gross Metabolic - body temperature increase
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Human - man
- DOSE/DURATION :
- 171 mg/kg/6D-I
- TOXIC EFFECTS :
- Behavioral - muscle weakness Musculoskeletal - other changes
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 940 mg/kg
- TOXIC EFFECTS :
- Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Gastrointestinal - hypermotility, diarrhea
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 910 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 1220 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 540 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- >500 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Unreported
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 1500 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 1370 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - guinea pig
- DOSE/DURATION :
- 1280 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - hamster
- DOSE/DURATION :
- 2400 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - hamster
- DOSE/DURATION :
- 1260 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Mammal - species unspecified
- DOSE/DURATION :
- 3 gm/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 7 gm/kg/14D-I
- TOXIC EFFECTS :
- Liver - changes in liver weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other transferases
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 3750 mg/kg/30D-C
- TOXIC EFFECTS :
- Liver - other changes Kidney, Ureter, Bladder - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 14 gm/kg/4W-I
- TOXIC EFFECTS :
- Liver - changes in liver weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 14700 mg/kg/7W-C
- TOXIC EFFECTS :
- Liver - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - catalases
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 1698 mg/kg/6D-C
- TOXIC EFFECTS :
- Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Metabolism (Intermediary) - lipids including transport
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - hamster
- DOSE/DURATION :
- 7 gm/kg/14D-I
- TOXIC EFFECTS :
- Liver - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other transferases
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 100 gm/kg/72W-C
- TOXIC EFFECTS :
- Tumorigenic - equivocal tumorigenic agent by RTECS criteria Gastrointestinal - tumors Liver - tumors
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 1050 mg/kg
- SEX/DURATION :
- female 16-22 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 14 gm/kg
- SEX/DURATION :
- female 2 week(s) pre-mating - 3 week(s) post-birth
- TOXIC EFFECTS :
- Reproductive - Effects on Newborn - biochemical and metabolic
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 5 gm/kg
- SEX/DURATION :
- female 6-15 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 3960 mg/kg
- SEX/DURATION :
- male 22 day(s) pre-mating
- TOXIC EFFECTS :
- Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Subcutaneous
- DOSE :
- 960 mg/kg
- SEX/DURATION :
- female 17 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Effects on Newborn - biochemical and metabolic
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Parenteral
- DOSE :
- 1440 mg/kg
- SEX/DURATION :
- female 14-17 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Effects on Embryo or Fetus - other effects to embryo
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 1300 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) Reproductive - Effects on Embryo or Fetus - fetal death
- TYPE OF TEST :
- DNA damage
- TYPE OF TEST :
- Unscheduled DNA synthesis
- TYPE OF TEST :
- Unscheduled DNA synthesis
- TYPE OF TEST :
- Unscheduled DNA synthesis
- TYPE OF TEST :
- Cytogenetic analysis
MUTATION DATA - TYPE OF TEST :
- Sister chromatid exchange
- TEST SYSTEM :
- Rodent - hamster Ovary
- DOSE/DURATION :
- 100 umol/L/1H
- REFERENCE :
- CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 5,703,1984 *** REVIEWS *** IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 24,39,1980 IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,391,1996 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 24,39,1980 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,391,1996 IARC Cancer Review:Group 3 IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,391,1996 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - T0426 No. of Facilities: 28 (estimated) No. of Industries: 1 No. of Occupations: 5 No. of Employees: 4648 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - T0426 No. of Facilities: 33 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 323 (estimated) No. of Female Employees: 176 (estimated)
- TYPE OF TEST :
- Sister chromatid exchange
- TEST SYSTEM :
- Rodent - hamster Ovary
- DOSE/DURATION :
- 100 umol/L/1H
- REFERENCE :
- CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980- Volume(issue)/page/year: 5,703,1984 *** REVIEWS *** IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 24,39,1980 IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,391,1996 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 24,39,1980 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,391,1996 IARC Cancer Review:Group 3 IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,391,1996 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - T0426 No. of Facilities: 28 (estimated) No. of Industries: 1 No. of Occupations: 5 No. of Employees: 4648 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - T0426 No. of Facilities: 33 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 323 (estimated) No. of Female Employees: 176 (estimated)
Safety Information
| Symbol | GHS05, GHS07 |
|---|---|
| Signal Word | Danger |
| Hazard Statements | H302-H315-H318-H335 |
| Precautionary Statements | P261-P280-P305 + P351 + P338 |
| Personal Protective Equipment | Eyeshields;Faceshields;full-face respirator (US);Gloves;multi-purpose combination respirator cartridge (US);type ABEK (EN14387) respirator filter |
| Hazard Codes | Xn:Harmful; |
| Risk Phrases | R22;R40 |
| Safety Phrases | S26-S36/37/39-S61-S45-S36/37 |
| RIDADR | UN 3082 9/PG 3 |
| WGK Germany | 3 |
| RTECS | UE9480000 |
| HS Code | 2918990090 |
Customs
| HS Code | 2918990090 |
|---|---|
| Summary | 2918990090. other carboxylic acids with additional oxygen function and their anhydrides, halides, peroxides and peroxyacids; their halogenated, sulphonated, nitrated or nitrosated derivatives. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0% |
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Synonyms
| ethyl 2-[(4-chlorophenyl)oxy]-2-methylpropanoate |
| MFCD00000615 |
| Ethyl α-(p-chlorophenoxy)isobutyrate |
| Ethyl p-chlorophenoxyisobutyrate |
| Ethyl α-(4-chlorophenoxy)isobutyrate |
| Clofipront |
| Clofibric Acid, Ethyl Ester |
| 2-(p-chlorophenoxy)isobutyric acid ethyl ester |
| Ethyl α-(4-chlorophenoxy)-α-methylpropionate |
| clofibrate |
| Atromid |
| Anparton |
| Clofibrato |
| Chlorfenisate |
| Ethyl 2-(4-chlorophenoxy)-2-methylpropanoate |
| Ethyl α-(p-chlorophenoxy)-α-methylpropionate |
| Sklerolip |
| Arterioflexin |
| Antilipid |
| Fibralem |
| ethyl p-chlorophenoxy-isobutyrate |
| Angiokapsul |
| Regelan N |
| EINECS 211-277-4 |
| Isobutyric acid, α-(p-chlorophenoxy)-, ethyl ester |
| Ethyl 2-(4-chlorophenoxy)isobutyrate |
| clofibric acid |
| Ethyl 2-(p-chlorophenoxy)-2-methylpropionate |
| Atromid-S |
| Propanoic acid, 2-(4-chlorophenoxy)-2-methyl-, ethyl ester |
| Regelan |
| Clofibratum |
| Ethyl 2-(4-chlorophenoxy)-2-methylpropionate |
