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99-66-1

99-66-1 structure
99-66-1 structure
  • Name: Valproic acid
  • Chemical Name: valproic acid
  • CAS Number: 99-66-1
  • Molecular Formula: C8H16O2
  • Molecular Weight: 144.211
  • Catalog: API Nervous system medication Antiepileptic and anticonvulsant
  • Create Date: 2018-09-24 18:12:25
  • Modify Date: 2024-01-02 17:15:35
  • Valproic acid is an HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2; Valproic acid sodium salt is used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches.

Name valproic acid
Synonyms Pentanoic acid, 2-propyl-
Mylproin
Ergenyl
MFCD00879852
2-Propylpentanoic acid
2-Propylvaleric Acid
Depakine
di-n-propyl-acetic acid
Valproic acid
Depakene
2-n-Propylpentanoic acid
Valproate
[3H]-Valproic acid
Convulex
Valeric acid, 2-propyl-
Valproic-250
2,2-BIS(TRIFLUOROMETHYL)PROPIONIC ACID
Dipropylacetic acid
[14C]-Valproic acid
2-propyl-pentanoic acid
EINECS 202-777-3
sodium valproate
Description Valproic acid is an HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2; Valproic acid sodium salt is used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches.
Related Catalog
Target

HDAC1:400 μM (IC50)

HDAC:0.5-2 mM (IC50)

HDAC2

Autophagy

Mitophagy

In Vitro Valproic acid inhibits the growth dose- and time-dependently with an IC50 of appr 10 and 4 mM at 24 and 72 h, respectively. Valproic acid significantly attenuates the activities of total, cytosol and nuclear HDACs. Valproic acid increases the form of acetylated histone 3 in HeLa cells. Valproic acid (1-3 mM) induces a G1 phase arrest, while 10 mM Valproic acid significantly induces a G2/M phase arrest of cell cycle in HeLa cells. In addition, Valproic acid increases the percentage of sub-G1 cells in HeLa cells in a dose-dependent manner at 24 h[1]. Valproic acid inhibits the mRNA and protein expression of VEGF, VEGFR2 and bFGF. Valproic acid inhibits the protein expression of HDAC1, increases histone H3 acetylation, and enhances the accumulation of hyperacetylated histone H3 on VEGF promoters[2]. Valproic acid treatment results in increased levels of phosphorylated AMPK/ACC in primary mouse hepatocytes. Phosphorylation of ACC following Valproic acid treatment is AMPK-dependent. Valproic acid inhibits the deacetylase activity of both mouse liver nuclear extracts and human recombinant HDAC1 while of the metabolites of Valproic acid, only 2-ene-Valproic acid and 4-ene-Valproic acid diminish deacetylase activity[4].
In Vivo Valproic acid (500 mg/kg, i.p.) inhibits the tumor growth and angiogenesisin the mice transplanted with Kasumi-1 cells. The IR rate in the Valproic acid group is 57.25% at the end of the experiment[2]. Valproic acid (350 mg/kg, i.p.) demonstrates more social investigation and play fighting than control animals[3].
Kinase Assay The activity of caspase-3, -8 and -9 is assessed using the caspase-3, -8 and -9 colorimetric assay kits, respectively. In brief, 1×106 cells in a 60-mm culture dish are incubated with 10 mM Valproic acid for 24 h. The cells are then washed in PBS and suspended in 5 volumes of lysis buffer provided with the kit. Protein concentrations are determined using the Bradford method. Supernatants containing 50 μg total protein are used to determine caspase-3, -8 and -9 activities. The supernatants are added to each well in 96-well microtiter plates with DEVD-pNA, IETD-pNA or LEHD-pNA as caspase-3, -8 and -9 substrates and the plates are incubated at 37°C for 1 h. The optical density of each well is measured at 405 nm using a microplate reader. The activity of caspase-3, -8 and -9 is expressed in arbitrary absorbance units.
Cell Assay In brief, 5×105 cells are seeded in 96-well microtiter plates for MTT assays. After exposure to the designated doses of Valproic acid for the indicated times, MTT solution [20 mL: 2 mg/mL in phosphate-buffered saline (PBS)] is added to each well of the 96-well plates. The plates are additionally incubated for 3 h at 37°C. Medium is withdrawn from the plates by pipetting and 200 mL DMSO is added to each well to solubilize the formazan crystals. The optical density is measured at 570 nm using a microplate reader.
Animal Admin Splenectomies are performed on the BALB/c nude mice. One week after the splenectomies, the mice receiv whole body irradiation with 137Cs at a dose of 4 Gy. At 48-72 h post-irradiation, the mice are subcutaneously implanted with Kasumi-1 cells (2×107 cells/mouse with 0.15-0.2 mL) in the right axillary region. The mice are randomLy assigned to two groups, the Valproic acid (n=6) and control (n=6) groups. When the tumors are appr 200 mm3 in size at appr 10 days post-implantation, 0.2 mL Valproic acid (500 mg/kg body weight) or 0.2 mL saline is injected intraperitoneally every day. Valproic acid is dissolved in saline at a concentration of 25 mg/mL. The longest diameter (a) and the shortest diameter (b) of the tumor are measured every three days, and the tumor volume (TV) is calculated according to the following formula: TV=1/2×a×b2. Following two weeks of injections, the mice are sacrificed by cervical dislocation and the tumor masses are removed for the following experiments.
References

[1]. Han BR, et al. Valproic acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis. Oncol Rep. 2013 Dec;30(6):2999-3005.

[2]. Zhang ZH, et al. Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi 1 leukemia cells. Mol Med Rep. 2013 Nov 28.

[3]. Cohen OS, et al. Acute prenatal exposure to a moderate dose of valproic acid increases social behavior and alters gene expression in rats. Int J Dev Neurosci. 2013 Dec;31(8):740-50.

[4]. Avery LB, et al. Valproic Acid Is a Novel Activator of AMP-Activated Protein Kinase and Decreases Liver Mass, Hepatic Fat Accumulation, and Serum Glucose in Obese Mice. Mol Pharmacol. 2014 Jan;85(1):1-10.

[5]. Valproic acid, et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem. 2001 Sep 28;276(39):36734-41.

Density 0.9±0.1 g/cm3
Boiling Point 220.0±0.0 °C at 760 mmHg
Melting Point 120 - 130ºC
Molecular Formula C8H16O2
Molecular Weight 144.211
Flash Point 111.1±0.0 °C
Exact Mass 144.115036
PSA 37.30000
LogP 2.72
Vapour Pressure 0.0±0.9 mmHg at 25°C
Index of Refraction 1.435
Water Solubility slightly soluble

CHEMICAL IDENTIFICATION

RTECS NUMBER :
YV7875000
CHEMICAL NAME :
Valeric acid, 2-propyl-
CAS REGISTRY NUMBER :
99-66-1
BEILSTEIN REFERENCE NO. :
1750447
LAST UPDATED :
199712
DATA ITEMS CITED :
43
MOLECULAR FORMULA :
C8-H16-O2
MOLECULAR WEIGHT :
144.24
WISWESSER LINE NOTATION :
QVY3&3

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - child
DOSE/DURATION :
375 mg/kg
TOXIC EFFECTS :
Cardiac - pulse rate increase, without fall in BP Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - cyanosis
REFERENCE :
CCMDC7 Critical Care Medicine. (Williams & Wilkins, 428 E. Preston Street, Baltimore, MD 21202) V.1- 1973- Volume(issue)/page/year: 21,299,1993
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - child
DOSE/DURATION :
412 mg/kg
TOXIC EFFECTS :
Behavioral - coma Cardiac - pulse rate increase, without fall in BP Lungs, Thorax, or Respiration - dyspnea
REFERENCE :
JATOD3 Journal of Analytical Toxicology. (Preston Pub. Inc., POB 48312, Niles, IL 60648) V.1- 1977- Volume(issue)/page/year: 20,55,1996
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - child
DOSE/DURATION :
10500 mg/kg/30W-I
TOXIC EFFECTS :
Gastrointestinal - changes in structure or function of endocrine pancreas Gastrointestinal - nausea or vomiting
REFERENCE :
AJDCAI American Journal of Diseases of Children. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1-80(3), 1911-50; V.100- 1960- Volume(issue)/page/year: 138,912,1984
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
21 mg/kg/2D-I
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity) Nutritional and Gross Metabolic - other changes
REFERENCE :
NEURAI Neurology. (Modern Medicine Pub., Inc., 1 E. First St., Duluth, MN 55802) V.1- 1951- Volume(issue)/page/year: 37,886,1987
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
SPECIES OBSERVED :
Human - child
DOSE/DURATION :
1800 mg/kg/60D
TOXIC EFFECTS :
Gastrointestinal - changes in structure or function of endocrine pancreas Gastrointestinal - nausea or vomiting
REFERENCE :
LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,1196,1980
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human
DOSE/DURATION :
13333 ug/kg/D-I
TOXIC EFFECTS :
Behavioral - sleep
REFERENCE :
NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 301,435,1979
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
670 mg/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea
REFERENCE :
FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 2,327,1964
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
1098 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: #78785
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
470 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
CHTPBA Chimica Therapeutica. (Paris, France) V.1-8, 1965-73. For publisher information, see EJMCA5. Volume(issue)/page/year: 3,430,1968
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
860 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
85GNAW "Pharmacodynamie de l'Acide Dipropylacetique (ou Propyl-2-Pentanoique) et de ses Amides," Carraz, G., Imprimerie Eymond, 1968 Volume(issue)/page/year: -,38,1968
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - rabbit
DOSE/DURATION :
1200 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
85GNAW "Pharmacodynamie de l'Acide Dipropylacetique (ou Propyl-2-Pentanoique) et de ses Amides," Carraz, G., Imprimerie Eymond, 1968 Volume(issue)/page/year: -,39,1968
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - guinea pig
DOSE/DURATION :
824 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
85GNAW "Pharmacodynamie de l'Acide Dipropylacetique (ou Propyl-2-Pentanoique) et de ses Amides," Carraz, G., Imprimerie Eymond, 1968 Volume(issue)/page/year: -,39,1968 ** REPRODUCTIVE DATA **
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
5480 mg/kg
SEX/DURATION :
female 1-39 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
REFERENCE :
AEPEDI Anales Espanoles de Pediatria. (Asociacion Espanola de Pediatria, Apartado 1176, 28028 Madrid, Spain) V.1- 1968- Volume(issue)/page/year: 39,19,1993
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
720 mg/kg
SEX/DURATION :
female 1-90 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - Central Nervous System
REFERENCE :
CPEDAM Clinical Pediatrics (Philadelphia). (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1962- Volume(issue)/page/year: 22,336,1983
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
6525 mg/kg
SEX/DURATION :
female 26 week(s) pre-mating female 1-36 week(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - biochemical and metabolic Reproductive - Effects on Newborn - physical
REFERENCE :
CPEDAM Clinical Pediatrics (Philadelphia). (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1962- Volume(issue)/page/year: 23,352,1984
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
126 gm/kg
SEX/DURATION :
female 1-18 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
FDTHES Fetal Diagnosis and Therapy (Basel). (S. Karger, Postfach. CH-4009 Basel, Switzerland) V.5- 1990- Volume(issue)/page/year: 9,155,1994
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
2394 mg/kg
SEX/DURATION :
female 1-36 week(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - Apgar score (human only)
REFERENCE :
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 219,768,1981
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
2047 mg/kg
SEX/DURATION :
female 27-40 week(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - physical
REFERENCE :
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 219,768,1981
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
5320 mg/kg
SEX/DURATION :
female 2-39 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)
REFERENCE :
JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 97,332,1980
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
5320 mg/kg
SEX/DURATION :
female 2-39 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - skin and skin appendages Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
REFERENCE :
JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 97,332,1980
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
5320 mg/kg
SEX/DURATION :
female 2-39 week(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)
REFERENCE :
JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 97,332,1980
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
600 mg/kg
SEX/DURATION :
female 13 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 - fetotoxicity (except death, e.g., stunted fetus)
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: 45,603,1992
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
34 gm/kg
SEX/DURATION :
male 60 day(s) pre-mating female 2 week(s) pre-mating - 1 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)
REFERENCE :
PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
2400 mg/kg
SEX/DURATION :
female 7-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - Central Nervous System
REFERENCE :
NETEEC Neurotoxicology and Teratology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.9- 1987- Volume(issue)/page/year: 13,471,1991
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
6 gm/kg
SEX/DURATION :
female 8-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - urogenital 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: 35,28A,1987
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
660 mg/kg
SEX/DURATION :
female 10 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - cytological changes (including somatic cell genetic material) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities
REFERENCE :
ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.32- 1974- Volume(issue)/page/year: 64,545,1990
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1500 mg/kg
SEX/DURATION :
female 6-15 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
432 mg/kg
SEX/DURATION :
female 11-13 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 Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)
REFERENCE :
TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 1,367,1981
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
432 mg/kg
SEX/DURATION :
female 8-10 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 :
TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 1,367,1981
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
519 mg/kg
SEX/DURATION :
female 8-10 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - Central Nervous System
REFERENCE :
TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 1,367,1981
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
600 mg/kg
SEX/DURATION :
female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)
REFERENCE :
AJMGDA American Journal of Medical Genetics. (John Wiley & Sons Ltd., 605 Third Ave., New York, NY 10158) V.1- 1977- Volume(issue)/page/year: 70,303,1997
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
2400 mg/kg
SEX/DURATION :
female 7-14 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - Central Nervous System
REFERENCE :
LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,763,1983
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
600 mg/kg
SEX/DURATION :
female 8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - other developmental abnormalities
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: 35,29A,1987
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
18 gm/kg
SEX/DURATION :
female 21-50 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetal death
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: 33,45A,1986
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
4550 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 - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)
REFERENCE :
PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
4550 mg/kg
SEX/DURATION :
female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
REFERENCE :
PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1950 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 :
PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
945 mg/kg
SEX/DURATION :
female 6-8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - urogenital system
REFERENCE :
36DLAV "Clinical and Pharmacological Aspects of Sodium Valproate (Epilim) in the Treatment of Epilepsy, Proceedings of a Symposium, Nottingham, UK, 1975," Legg, N.J., et al., eds., Kent, UK, MCS Consultants, 1976 Volume(issue)/page/year: -,105,1976
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
300 mg/kg
SEX/DURATION :
female 7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - Central Nervous 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: 29(2),47A,1984 *** REVIEWS *** TOXICOLOGY REVIEW JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 97,333,1980 TOXICOLOGY REVIEW PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 2,58,1979 TOXICOLOGY REVIEW APJUA8 Acta Pharmaceutica Jugoslavica. (FDH, Masarykova 2, 41000 Zagreb, Yugoslavia) V.1-41, 1951-1991. Volume(issue)/page/year: 41,79,1991 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3895 No. of Facilities: 245 (estimated) No. of Industries: 4 No. of Occupations: 6 No. of Employees: 5848 (estimated) No. of Female Employees: 3255 (estimated)
Symbol GHS07 GHS08
GHS07, GHS08
Signal Word Danger
Hazard Statements H302-H315-H319-H335-H360
Precautionary Statements P201-P280-P301 + P312 + P330-P305 + P351 + P338-P308 + P313
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;R36/37/38
Safety Phrases S26-S45-S36/37-S16
RIDADR UN 1230 3/PG 2
WGK Germany 3
RTECS YV7875000
Packaging Group III
Hazard Class 8
HS Code 2915600000
HS Code 2915900090
Summary 2915900090 other saturated acyclic monocarboxylic acids and their anhydrides, halides, peroxides and peroxyacids; their halogenated, sulphonated, nitrated or nitrosated derivatives VAT:17.0% Tax rebate rate:9.0% Supervision conditions:AB(certificate of inspection for goods inward,certificate of inspection for goods outward) MFN tariff:5.5% General tariff:30.0%