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53-86-1

53-86-1 structure
53-86-1 structure

Name indometacin
Synonyms Lausit
Catlep
Tannex
Bonidin
Indometacin
Indacin
Amuno
Inacid
1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetic Acid
EINECS 200-186-5
Dolovin
MFCD00057095
Indomethacin
INDOCIN
Vonum
2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetic acid
Description Indomethacin is a potent and nonselective inhibitor of COX1 and COX2, with IC50s of 18 nM and 26 nM for human COX-1 and COX-2, respectively, in CHO cells.
Related Catalog
Target

Human COX-1:18 nM (IC50, in CHO cells)

Human COX-2:26 nM (IC50, in CHO cells)

In Vitro Indomethacin is a potent and nonselective inhibitor of COX1 and COX2, with IC50s of 18 nM and 26 nM for human COX-1 and COX-2, respectively, in CHO cells. Indomethacin inhibits lipopolysaccharide (LPS)-induced PGE2 production (COX-2) in a human whole blood assay with a potency (IC50=0.68±0.17 μM), and suppresses coagulation-induced TXB2 production (COX-1) (IC50=0.19±0.02 μM). Indomethacin blocks COX-1 with an IC50 of 20±1 nM in U937 cell microsomes at a low arachidonic acid concentration (0.1 μM)[1].
In Vivo Indomethacin dose-dependently inhibits both the carrageenan-induced rat paw oedema (ED50, 2.0 mg/kg), hyperalgesia (ED50, 1.5 mg/kg), and is also effective at reversing LPS-induced pyrexia in rats (ED50, 1.1 mg/kg)[1]. Indomethacin (2.5 mg/kg, i.p) decreases the number of NeuN+ cells in the animals at 8 days after ET-1 injection. Indomethacin also reduces microglia/macrophage activation at 14 days. Indomethacin significantly increases the number of SVZ DCX+ cells/field at 14 days post stroke[2]. Indomethacin (22.9 mg/kg, p.o.) produces 8 to 10 linear mucosal lesions extended from the fundic to pyloric area of stomach wall[3].
Animal Admin Rats[2] To investigate the effects of Indomethacin treatment on both microglia activation, neuroprotection and adult neurogenesis, rats are divided in four experimental groups: animals injected with ET-1, treated with sterile saline (i.p.) for 7 days and perfused at 8 days following ET-1 injection (group 1, n=4); animals injected with ET-1, treated with Indomethacin (2.5 mg/kg, i.p) for 7 days and perfused at 8 days following ET-1 injection (group 2, n=4); animals injected with ET-1, treated with sterile saline (i.p.) for 7 days and perfused at 14 days following ET-1 injection (group 3, n=4); animals injected with ET-1, treated with Indomethacin (2.5 mg/kg, i.p) for 7 days and perfused at 14 days following ET-1 injection (group 4, n=4). After survival times of 7 or 14 days, animals are deeply anesthetized with a mixture of ketamine hydrochloride (72 mg/kg, i.p.) and xylazine hydrochloride (9 mg/kg, i.p.). After the verification of complete absence of both the corneal and the paw withdraw reflexes, the animals are transcardially perfused with heparinized 0.9% warm phosphate-buffered saline (PBS) followed by 4% cold paraformaldehyde in 0.1 M phosphate buffer (PB), pH 7.4. Brains are post-fixed for 24 h in the same fixative and cryoprotected in different gradients of sucrose-glycerol solutions over 7 days. The tissue is then frozen in an embedding medium, and cut at 30 μM in the coronal plane using a cryostat. Sections are then mounted onto gelatinized slides and stored in a freezer at −20°C[2].
References

[1]. Riendeau D, et al. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. Br J Pharmacol. 1997 May;121(1):105-17.

[2]. Lopes RS, et al. Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia. J Biosci. 2016 Sep;41(3):381-94.

[3]. Afroz S, et al. Concentrated phosphatidic acid in cereal brans as potential protective agents against indomethacin-induced stomach ulcer. J Agric Food Chem. 2016 Aug 26.

[4]. Qixiong Zhang, et al. Structure-Property Correlations of Reactive Oxygen Species-Responsive and Hydrogen Peroxide-Eliminating Materials with Anti-Oxidant and Anti-Inflammatory Activities. Chem Mater. 2017, 29(19):8221-8238.

Density 1.32g/cm3
Boiling Point 499.4ºC at 760 mmHg
Melting Point 155-162 °C
Molecular Formula C19H16ClNO4
Molecular Weight 357.78800
Flash Point 255.8ºC
Exact Mass 357.07700
PSA 68.53000
LogP 3.92730
Stability Stable. Incompatible with strong oxidizing agents.
Water Solubility ethanol: 50 mg/mL, clear, yellow-green

CHEMICAL IDENTIFICATION

RTECS NUMBER :
NL3500000
CHEMICAL NAME :
Indole-3-acetic acid, 1-(p-chlorobenzoyl)-5-methoxy-2-methyl-
CAS REGISTRY NUMBER :
53-86-1
BEILSTEIN REFERENCE NO. :
0497341
LAST UPDATED :
199703
DATA ITEMS CITED :
125
MOLECULAR FORMULA :
C19-H16-Cl-N-O4
MOLECULAR WEIGHT :
357.81
WISWESSER LINE NOTATION :
T56 BNJ BVR CG& C1 D1VQ GO1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
4286 ug/kg/2D-I
TOXIC EFFECTS :
Skin and Appendages - dermatitis, other (after systemic exposure)
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
15 mg/kg/2W-I
TOXIC EFFECTS :
Blood - aplastic anemia
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - infant
DOSE/DURATION :
400 ug/kg/2D-I
TOXIC EFFECTS :
Gastrointestinal - necrotic changes
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
2098 ug/kg/1D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - urine volume decreased
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
22500 ug/kg/3W-I
TOXIC EFFECTS :
Liver - hepatitis, fibrous (cirrhosis, post-necrotic scarring) Liver - other changes
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human
DOSE/DURATION :
113 mg/kg/8W-I
TOXIC EFFECTS :
Gastrointestinal - hypermotility, diarrhea Gastrointestinal - other changes
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Human - infant
DOSE/DURATION :
200 ug/kg
TOXIC EFFECTS :
Blood - hemorrhage
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
499 mg/kg/87W-I
TOXIC EFFECTS :
Behavioral - stiffness Kidney, Ureter, Bladder - hematuria
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Rectal
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
2586 mg/kg/3.5Y-I
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - retinal changes (pigmentary depositions, retinitis, other)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Multiple routes
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
3557 mg/kg/5Y-I
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) - retinal changes (pigmentary depositions, retinitis, other)
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
2420 ug/kg
TOXIC EFFECTS :
Gastrointestinal - ulceration or bleeding from stomach
TYPE OF TEST :
LD - Lethal dose
ROUTE OF EXPOSURE :
Administration onto the skin
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
>250 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 - rat
DOSE/DURATION :
13 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 :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
12 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 - rat
DOSE/DURATION :
21 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 :
Intramuscular
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
26300 ug/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 :
Rectal
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
31900 ug/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 :
11841 ug/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 :
10 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 :
Subcutaneous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
18300 ug/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 :
30 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 :
Intramuscular
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
18200 ug/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 - dog
DOSE/DURATION :
160 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 :
Mammal - dog
DOSE/DURATION :
100 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 - cat
DOSE/DURATION :
320 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Mammal - cat
DOSE/DURATION :
20200 ug/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 :
135 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 :
100 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
TYPE OF TEST :
LD - Lethal dose
ROUTE OF EXPOSURE :
Administration onto the skin
SPECIES OBSERVED :
Rodent - guinea pig
DOSE/DURATION :
>100 mg/kg
TOXIC EFFECTS :
Behavioral - excitement
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - guinea pig
DOSE/DURATION :
143 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 - guinea pig
DOSE/DURATION :
180 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 :
81 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 :
8 mg/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 :
33 mg/kg/11D-I
TOXIC EFFECTS :
Gastrointestinal - ulceration or bleeding from stomach Gastrointestinal - ulceration or bleeding from duodenum Gastrointestinal - other changes
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
168 mg/kg/4W-C
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - changes in lung weight Endocrine - changes in spleen weight Blood - normocytic anemia
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
273 mg/kg/13W-I
TOXIC EFFECTS :
Blood - normocytic anemia Biochemical - Metabolism (Intermediary) - other proteins Related to Chronic Data - death
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
1820 mg/kg/52W-C
TOXIC EFFECTS :
Gastrointestinal - ulceration or bleeding from small intestine Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
210 mg/kg/35D-C
TOXIC EFFECTS :
Gastrointestinal - ulceration or bleeding from stomach Endocrine - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
650 mg/kg/26W-I
TOXIC EFFECTS :
Behavioral - food intake (animal) Gastrointestinal - ulceration or bleeding from small intestine Nutritional and Gross Metabolic - weight loss or decreased weight gain
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
105 mg/kg/21D-I
TOXIC EFFECTS :
Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight Related to Chronic Data - changes in ovarian weight
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
24 mg/kg/4D-I
TOXIC EFFECTS :
Gastrointestinal - ulceration or bleeding from stomach
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
150 mg/kg/5W-I
TOXIC EFFECTS :
Lungs, Thorax, or Respiration - other changes Blood - changes in spleen Related to Chronic Data - death
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
90 mg/kg/90D-C
TOXIC EFFECTS :
Gastrointestinal - ulceration or bleeding from stomach Gastrointestinal - ulceration or bleeding from small intestine Gastrointestinal - hypermotility, diarrhea
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
350 mg/kg/5W-I
TOXIC EFFECTS :
Gastrointestinal - ulceration or bleeding from large intestine Kidney, Ureter, Bladder - other changes in urine composition Related to Chronic Data - death
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Primate - monkey
DOSE/DURATION :
135 mg/kg/90D-C
TOXIC EFFECTS :
Gastrointestinal - ulceration or bleeding from stomach Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Blood - changes in leukocyte (WBC) count
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Mammal - species unspecified
DOSE/DURATION :
168 mg/kg/4W-I
TOXIC EFFECTS :
Gastrointestinal - necrotic changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - changes in chlorine
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
644 mg/kg/92W-C
TOXIC EFFECTS :
Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1500 ug/kg
SEX/DURATION :
female 36 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - respiratory system Reproductive - Effects on Newborn - other neonatal measures or effects
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1500 mg/kg
SEX/DURATION :
female 27 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
12 mg/kg
SEX/DURATION :
female 33-34 week(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - stillbirth
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
525 mg/kg
SEX/DURATION :
female 16-32 week(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition Reproductive - Maternal Effects - other effects Reproductive - Specific Developmental Abnormalities - urogenital system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
DOSE :
18 mg/kg
SEX/DURATION :
female 33-34 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - homeostasis
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
6 mg/kg
SEX/DURATION :
female 39 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - urogenital system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
4 mg/kg
SEX/DURATION :
female 10 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - urogenital system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
2 mg/kg
SEX/DURATION :
female 28 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Specific Developmental Abnormalities - homeostasis
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
12 mg/kg
SEX/DURATION :
female 32 week(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - stillbirth
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
14 mg/kg
SEX/DURATION :
female 34 week(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Newborn - other neonatal measures or effects
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Multiple routes
DOSE :
22 mg/kg
SEX/DURATION :
female 33 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Effects on Newborn - Apgar score (human only)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Rectal
DOSE :
12 mg/kg
SEX/DURATION :
female 28 week(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - blood and lymphatic systems (including spleen and marrow) Reproductive - Specific Developmental Abnormalities - gastrointestinal system Reproductive - Specific Developmental Abnormalities - urogenital system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1 mg/kg
SEX/DURATION :
female 21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
300 ug/kg
SEX/DURATION :
female 21-22 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - live birth index (measured after birth)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
10 mg/kg
SEX/DURATION :
female 17-22 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - respiratory system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
12 mg/kg
SEX/DURATION :
female 5-16 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 :
20 mg/kg
SEX/DURATION :
female 1-21 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 - other developmental abnormalities
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
2500 ug/kg
SEX/DURATION :
female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
28 mg/kg
SEX/DURATION :
male 7 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
4150 ug/kg
SEX/DURATION :
female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
5 mg/kg
SEX/DURATION :
female 5 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
2500 ug/kg
SEX/DURATION :
female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
12 mg/kg
SEX/DURATION :
female 3-4 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
9 mg/kg
SEX/DURATION :
female 9 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - other effects
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Parenteral
DOSE :
3 mg/kg
SEX/DURATION :
female 19-21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Specific Developmental Abnormalities - respiratory system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
3 mg/kg
SEX/DURATION :
female 20 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intrauterine
DOSE :
500 ug/kg
SEX/DURATION :
female 4 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravaginal
DOSE :
125 mg/kg
SEX/DURATION :
female 7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
10 mg/kg
SEX/DURATION :
female 7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - eye/ear
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
10 mg/kg
SEX/DURATION :
female 7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
4 mg/kg
SEX/DURATION :
female 13 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
9 mg/kg
SEX/DURATION :
female 2 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
40 mg/kg
SEX/DURATION :
female 8-15 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 - body wall
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
40 mg/kg
SEX/DURATION :
female 8-15 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
8 mg/kg
SEX/DURATION :
female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Parenteral
DOSE :
8 mg/kg
SEX/DURATION :
female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
496 mg/kg
SEX/DURATION :
female 21-26 week(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - physical
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
747 mg/kg
SEX/DURATION :
female 21-26 week(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
6 mg/kg
SEX/DURATION :
female 2 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
96 mg/kg
SEX/DURATION :
female 20-31 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
10 mg/kg
SEX/DURATION :
female 29 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
6 mg/kg
SEX/DURATION :
female 2 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
1590 ug/kg
SEX/DURATION :
female 6 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - maternal-fetal exchange
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
48 mg/kg
SEX/DURATION :
female 23-28 day(s) after conception
TOXIC EFFECTS :
Reproductive - Maternal Effects - parturition
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
32 mg/kg
SEX/DURATION :
female 5-6 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
24 mg/kg
SEX/DURATION :
female 4-7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
64 mg/kg
SEX/DURATION :
female 9-12 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
20 mg/kg
SEX/DURATION :
female 26-29 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
DOSE :
148 mg/kg
SEX/DURATION :
female 1-9 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
DOSE :
20 mg/kg
SEX/DURATION :
female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
DOSE :
20 mg/kg
SEX/DURATION :
female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
7500 ug/kg
SEX/DURATION :
female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
5500 ug/kg
SEX/DURATION :
female 1-3 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
30 mg/kg
SEX/DURATION :
female 24-26 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - respiratory system Reproductive - Effects on Newborn - biochemical and metabolic
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Parenteral
DOSE :
2500 ng/kg
SEX/DURATION :
female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
160 mg/kg
SEX/DURATION :
female 16 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
240 mg/kg
SEX/DURATION :
female 12 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - menstrual cycle changes or disorders
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intrauterine
DOSE :
66640 ug/kg
SEX/DURATION :
female 9 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - menstrual cycle changes or disorders
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
144 mg/kg
SEX/DURATION :
female 18 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - other effects
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
DOSE :
40 ug/kg
SEX/DURATION :
female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Fertility - other measures of fertility
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1 mg/kg
SEX/DURATION :
female 21 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system
TYPE OF TEST :
Mutation test systems - not otherwise specified
TYPE OF TEST :
Dominant lethal test
TYPE OF TEST :
Micronucleus test
TYPE OF TEST :
Micronucleus test
TYPE OF TEST :
DNA inhibition
TYPE OF TEST :
Cytogenetic analysis
TYPE OF TEST :
Sperm Morphology

MUTATION DATA

TEST SYSTEM :
Rodent - mouse
DOSE/DURATION :
60 mg/kg/5D (Continuous)
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 188,343,1987 *** REVIEWS *** TOXICOLOGY REVIEW CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 17,85,1980 TOXICOLOGY REVIEW REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987- Volume(issue)/page/year: 9,7,1995 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4091 No. of Facilities: 123 (estimated) No. of Industries: 2 No. of Occupations: 10 No. of Employees: 5082 (estimated) No. of Female Employees: 2130 (estimated)
Symbol GHS06
GHS06
Signal Word Danger
Hazard Statements H300
Precautionary Statements Missing Phrase - N15.00950417
Personal Protective Equipment Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges
Hazard Codes T+:Verytoxic;
Risk Phrases R28
Safety Phrases S28-S36/37-S45
RIDADR UN 2811 6.1/PG 1
WGK Germany 3
RTECS NL3500000
Packaging Group I
Hazard Class 6.1
HS Code 2933290090
HS Code 2933990090
Summary 2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%