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50-63-5, Chloroquine diphosphate

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 Chloroquine diphosphate Biological Activity

Description Chloroquine (diphosphate) is an antimalarial and anti-inflammatory drug widely used to treat malaria and rheumatoid arthritis. Chloroquine is an inhibitor of autophagy and toll-like receptors (TLRs).
Related Catalog
Target

Autophagy, TLRs[1][2][3]

In Vitro Chloroquine (CHQ, 20 μM) inhibits IL-12p70 release and reduces Th1-priming capacity of activated human monocyte-derived Langerhans-like cells (MoLC). Chloroquine (CHQ, 20 μM) enhances IL-1–induced IL-23 secretion in MoLC and subsequently increases IL-17A release by primed CD4+ T cells[1]. Chloroquine (25 μM) suppresses MMP-9 mRNA expression in normoxia and hypoxia in parental MDA-MB-231 cells. Chloroquine has cell-, dose- and hypoxia-dependent effects on MMP-2, MMP-9 and MMP-13 mRNA expression[2]. TLR7 and TLR9 inhibition using IRS-954 or chloroquine significantly reduces HuH7 cell proliferation in vitro[3].
In Vivo Chloroquine (80 mg/kg, i.p.) does not prevent the growth of the triple-negative MDA-MB-231 cells with high or low TLR9 expression levels in the orthotopic mouse model[2]. TLR7 and TLR9 inhibition using IRS-954 or chloroquine significantly inhibits tumour growth in the mouse xenograft model. HCC development in the DEN/NMOR rat model is also significantly inhibited by chloroquine[3].
Cell Assay The cells are cultured in 6-well plates with normal culture medium in the presence of vehicle or 25 or 50 μM chloroquine, until near confluency, after which they are rinsed with sterile phosphate-buffered saline (PBS) and cultured further for the indicated times in serum-free culture medium. At the desired time-points, the culture medium is discarded and the cells are quickly harvested in lysis buffer and clarified by centrifugation. Subsequent to boiling the supernatants in reducing sodium dodecyl sulphate (SDS) sample buffer, equal amounts of protein (100 μg) are loaded per lane and the samples are electrophoresed into 10 or 4-20% gradient polyacrylamide SDS gels, then transferred to a nitrocellulose membrane. To detect TLR9, the blots are incubated overnight at 4°C with anti-TLR9 antibodies, diluted 1:500 in Tris-buffered saline with 0.1% (v/v) Tween-20 (TBST). Equal loading is confirmed with polyclonal rabbit anti-actin. Secondary detection is performed with horseradish peroxidase-linked secondary antibodies. The protein bands are visualized by chemiluminescence using an ECL kit.
Animal Admin Control and TLR9 siRNA MDA-MB-231 cells (5×105 cells in 100 μL) are inoculated into the mammary fat pads of four-week-old, immune-deficient mice (athymic nude/nu Foxn1). Treatments are started seven days after tumor cell inoculation. The mice are treated daily either with intraperitoneal (i.p.) chloroquine (80 mg/kg) or vehicle (PBS). The animals are monitored daily for clinical signs. Tumor measurements are performed twice a week and tumor volume is calculated according to the formula V=(π/6) (d1×d2)3/2, where d1 and d2 are perpendicular tumor diameters. The tumors are allowed to grow for 22 days, at which point the mice are sacrificed and the tumors are dissected for a final measurement. Throughout the experiments, the animals are maintained under controlled pathogen-free environmental conditions (20-21°C, 30-60% relative humidity and a 12-h lighting cycle). The mice are fed with small-animal food pellets and supplied with sterile water ad libitum.
References

[1]. Said A, et al. Chloroquine promotes IL-17 production by CD4+ T cells via p38-dependent IL-23 release by monocyte-derived Langerhans-like cells. J Immunol. 2014 Dec 15;193(12):6135-43.

[2]. Tuomela J, et al. Chloroquine has tumor-inhibitory and tumor-promoting effects in triple-negative breast cancer. Oncol Lett. 2013 Dec;6(6):1665-1672.

[3]. Mohamed FE, et al. Effect of toll-like receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma. Liver Int. 2014 Jul 2. doi: 10.1111/liv.12626.

 Chemical & Physical Properties

Boiling Point 460.6ºC at 760 mmHg
Melting Point 200 °C (dec.)(lit.)
Molecular Formula C18H32ClN3O8P2
Molecular Weight 515.862
Flash Point 232.3ºC
Exact Mass 515.135315
PSA 203.30000
LogP 3.02640
Storage condition Desiccate at RT
Water Solubility H2O: 50 mg/mL, clear

 Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :
VB2450000
CHEMICAL NAME :
Quinoline, 7-chloro-4-(4-diethylamino-1-methyl-butylamino)-, diphosphate
CAS REGISTRY NUMBER :
50-63-5
LAST UPDATED :
199606
DATA ITEMS CITED :
30
MOLECULAR FORMULA :
C18-H26-Cl-N3.2H3-O4-P
MOLECULAR WEIGHT :
515.92
WISWESSER LINE NOTATION :
T66 BNJ EMY1&3N2&2 IG &P2-O6

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human – man
DOSE/DURATION :
8571 ug/kg
TOXIC EFFECTS :
Gastrointestinal – nausea or vomiting Gastrointestinal – other changes
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human – man
DOSE/DURATION :
8571 ug/kg
TOXIC EFFECTS :
Gastrointestinal – ulceration or bleeding from duodenum Gastrointestinal – nausea or vomiting Gastrointestinal – other changes
TYPE OF TEST :
LDLo – Lowest published lethal dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human – child
DOSE/DURATION :
250 mg/kg
TOXIC EFFECTS :
Behavioral – coma
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human – woman
DOSE/DURATION :
167 mg/kg
TOXIC EFFECTS :
Cardiac – EKG changes not diagnostic of specified effects Vascular – BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration – respiratory depression
TYPE OF TEST :
LDLo – Lowest published lethal dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human – man
DOSE/DURATION :
179 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 :
Oral
SPECIES OBSERVED :
Rodent – rat
DOSE/DURATION :
600 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 :
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 :
Intraperitoneal
SPECIES OBSERVED :
Rodent – mouse
DOSE/DURATION :
68 mg/kg
TOXIC EFFECTS :
Behavioral – convulsions or effect on seizure threshold
TYPE OF TEST :
LD50 – Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent – mouse
DOSE/DURATION :
200 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 – dog
DOSE/DURATION :
8 mg/kg
TOXIC EFFECTS :
Behavioral – somnolence (general depressed activity)
TYPE OF TEST :
LD50 – Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Bird – domestic
DOSE/DURATION :
64500 ug/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 :
8820 mg/kg/21W-C
TOXIC EFFECTS :
Cardiac – other changes Liver – hepatitis (hepatocellular necrosis), diffuse Related to Chronic Data – death
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent – rat
DOSE/DURATION :
840 mg/kg/21D-I
TOXIC EFFECTS :
Behavioral – food intake (animal) Kidney, Ureter, Bladder – urine volume decreased Nutritional and Gross Metabolic – weight loss or decreased weight gain
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent – rat
DOSE/DURATION :
400 mg/kg/10D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder – proteinuria Kidney, Ureter, Bladder – other changes in urine composition Biochemical – Enzyme inhibition, induction, or change in blood or tissue levels – phosphatases
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Ocular
SPECIES OBSERVED :
Rodent – rat
DOSE/DURATION :
72 ug/kg/12D-I
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) – corneal damage
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Mammal – dog
DOSE/DURATION :
280 mg/kg/14D-I
TOXIC EFFECTS :
Behavioral – tremor Related to Chronic Data – death
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Primate – monkey
DOSE/DURATION :
1 gm/kg/10D-I
TOXIC EFFECTS :
Liver – fatty liver degeneration 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
DOSE :
1200 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 :
550 mg/kg
SEX/DURATION :
female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive – Specific Developmental Abnormalities – eye/ear
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
750 mg/kg
SEX/DURATION :
female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive – Effects on Embryo or Fetus – fetal death
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
80 mg/kg
SEX/DURATION :
female 20-21 day(s) after conception
TOXIC EFFECTS :
Reproductive – Specific Developmental Abnormalities – respiratory system Reproductive – Effects on Newborn – physical
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
475 mg/kg
SEX/DURATION :
female 10-14 day(s) after conception
TOXIC EFFECTS :
Reproductive – Effects on Newborn – physical

MUTATION DATA

TYPE OF TEST :
Sister chromatid exchange
TEST SYSTEM :
Rodent – hamster Lung
DOSE/DURATION :
100 ug/L
REFERENCE :
CBTOE2 Cell Biology and Toxicology. (Princeton Scientific Pub., Inc., 301 N. Harrison St., CN 5279, Princeton, NJ 08540) V.1- 1984- Volume(issue)/page/year: 2,379,1986 *** REVIEWS *** TOXICOLOGY REVIEW INTEAG Internist. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1960- Volume(issue)/page/year: 15,7,1974 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES – National Occupational Exposure Survey (1983) NOES Hazard Code – X4486 No. of Facilities: 40 (estimated) No. of Industries: 2 No. of Occupations: 3 No. of Employees: 644 (estimated) No. of Female Employees: 238 (estimated)

 Safety Information

Symbol GHS07
GHS07
Signal Word Warning
Hazard Statements H302
Precautionary Statements P301 + P312 + P330
Personal Protective Equipment dust mask type N95 (US);Eyeshields;Gloves
Hazard Codes Xn:Harmful;
Risk Phrases R22
Safety Phrases S22-S24/25
RIDADR 1544
WGK Germany 3
RTECS VB2450000
Packaging Group III
Hazard Class 6.1(b)
HS Code 2933499090

 Precursor & DownStream

Precursor  0
DownStream  1

 Customs

HS Code 2933499090
Summary 2933499090. other compounds containing in the structure a quinoline or isoquinoline ring-system (whether or not hydrogenated), not further fused. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

 Articles108

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Given the diversity of autophagy targets and regulation, it is important to characterize autophagy in various cell types and conditions. We used a primary myocyte cell culture system to assay the role…

An integrated biological approach to guide the development of metal-chelating inhibitors of influenza virus PA endonuclease.

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 Synonyms

MFCD00069852
acide phosphorique – N-(7-chloroquinoléin-4-yl)-N,N-diéthylpentane-1,4-diamine (2:1)
Chloroquine phosphate
7-Chloro-4-[4-(diethylamino)-1-methylbutylamino]quinoline Diphosphate
EINECS 200-055-2
N-(7-chloroquinolin-4-yl)-N,N-diethylpentane-1,4-diamine bis(phosphate)
N4-(7-chloroquinolin-4-yl)-N1,N1-diethylpentane-1,4-diamine phosphate (1:2)
N-(7-Chloro-4-quinolinyl)-N,N-diethyl-1,4-pentanediamine phosphate (1:2)
N4-(7-Chloro-4-quinolyl)-N1,N1-diethyl-1,4-pentanediamine Diphosphate
Chloroquine diphosphate salt
7-Chloro-4-((4-(diethylamino)-1-methylbutyl)amino)quinoline phosphate (1:2)
Aralen phosphate
1,4-Pentanediamine, N-(7-chloro-4-quinolinyl)-N,N-diethyl-, phosphate (1:2)
1,4-pentanediamine, N4-(7-chloro-4-quinolinyl)-N1,N1-diethyl-, phosphate (1:2)
N-(7-Chloroquinolin-4-yl)-N,N-diethylpentane-1,4-diamine phosphate (1:2)
Chloroquine diphosphate
Imagon
Tresochin
Chloroquinediphosphate
Malaquin
Phosphorosäure–N-(7-chlorchinolin-4-yl)-N,N-diethylpentan-1,4-diamin(2:1)

 

 Chloroquine diphosphate Biological Activity

Description Chloroquine (diphosphate) is an antimalarial and anti-inflammatory drug widely used to treat malaria and rheumatoid arthritis. Chloroquine is an inhibitor of autophagy and toll-like receptors (TLRs).
Related Catalog
Target

Autophagy, TLRs[1][2][3]

In Vitro Chloroquine (CHQ, 20 μM) inhibits IL-12p70 release and reduces Th1-priming capacity of activated human monocyte-derived Langerhans-like cells (MoLC). Chloroquine (CHQ, 20 μM) enhances IL-1–induced IL-23 secretion in MoLC and subsequently increases IL-17A release by primed CD4+ T cells[1]. Chloroquine (25 μM) suppresses MMP-9 mRNA expression in normoxia and hypoxia in parental MDA-MB-231 cells. Chloroquine has cell-, dose- and hypoxia-dependent effects on MMP-2, MMP-9 and MMP-13 mRNA expression[2]. TLR7 and TLR9 inhibition using IRS-954 or chloroquine significantly reduces HuH7 cell proliferation in vitro[3].
In Vivo Chloroquine (80 mg/kg, i.p.) does not prevent the growth of the triple-negative MDA-MB-231 cells with high or low TLR9 expression levels in the orthotopic mouse model[2]. TLR7 and TLR9 inhibition using IRS-954 or chloroquine significantly inhibits tumour growth in the mouse xenograft model. HCC development in the DEN/NMOR rat model is also significantly inhibited by chloroquine[3].
Cell Assay The cells are cultured in 6-well plates with normal culture medium in the presence of vehicle or 25 or 50 μM chloroquine, until near confluency, after which they are rinsed with sterile phosphate-buffered saline (PBS) and cultured further for the indicated times in serum-free culture medium. At the desired time-points, the culture medium is discarded and the cells are quickly harvested in lysis buffer and clarified by centrifugation. Subsequent to boiling the supernatants in reducing sodium dodecyl sulphate (SDS) sample buffer, equal amounts of protein (100 μg) are loaded per lane and the samples are electrophoresed into 10 or 4-20% gradient polyacrylamide SDS gels, then transferred to a nitrocellulose membrane. To detect TLR9, the blots are incubated overnight at 4°C with anti-TLR9 antibodies, diluted 1:500 in Tris-buffered saline with 0.1% (v/v) Tween-20 (TBST). Equal loading is confirmed with polyclonal rabbit anti-actin. Secondary detection is performed with horseradish peroxidase-linked secondary antibodies. The protein bands are visualized by chemiluminescence using an ECL kit.
Animal Admin Control and TLR9 siRNA MDA-MB-231 cells (5×105 cells in 100 μL) are inoculated into the mammary fat pads of four-week-old, immune-deficient mice (athymic nude/nu Foxn1). Treatments are started seven days after tumor cell inoculation. The mice are treated daily either with intraperitoneal (i.p.) chloroquine (80 mg/kg) or vehicle (PBS). The animals are monitored daily for clinical signs. Tumor measurements are performed twice a week and tumor volume is calculated according to the formula V=(π/6) (d1×d2)3/2, where d1 and d2 are perpendicular tumor diameters. The tumors are allowed to grow for 22 days, at which point the mice are sacrificed and the tumors are dissected for a final measurement. Throughout the experiments, the animals are maintained under controlled pathogen-free environmental conditions (20-21°C, 30-60% relative humidity and a 12-h lighting cycle). The mice are fed with small-animal food pellets and supplied with sterile water ad libitum.
References

[1]. Said A, et al. Chloroquine promotes IL-17 production by CD4+ T cells via p38-dependent IL-23 release by monocyte-derived Langerhans-like cells. J Immunol. 2014 Dec 15;193(12):6135-43.

[2]. Tuomela J, et al. Chloroquine has tumor-inhibitory and tumor-promoting effects in triple-negative breast cancer. Oncol Lett. 2013 Dec;6(6):1665-1672.

[3]. Mohamed FE, et al. Effect of toll-like receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma. Liver Int. 2014 Jul 2. doi: 10.1111/liv.12626.

 Chemical & Physical Properties

Boiling Point 460.6ºC at 760 mmHg
Melting Point 200 °C (dec.)(lit.)
Molecular Formula C18H32ClN3O8P2
Molecular Weight 515.862
Flash Point 232.3ºC
Exact Mass 515.135315
PSA 203.30000
LogP 3.02640
Storage condition Desiccate at RT
Water Solubility H2O: 50 mg/mL, clear

 Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :
VB2450000
CHEMICAL NAME :
Quinoline, 7-chloro-4-(4-diethylamino-1-methyl-butylamino)-, diphosphate
CAS REGISTRY NUMBER :
50-63-5
LAST UPDATED :
199606
DATA ITEMS CITED :
30
MOLECULAR FORMULA :
C18-H26-Cl-N3.2H3-O4-P
MOLECULAR WEIGHT :
515.92
WISWESSER LINE NOTATION :
T66 BNJ EMY1&3N2&2 IG &P2-O6

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human – man
DOSE/DURATION :
8571 ug/kg
TOXIC EFFECTS :
Gastrointestinal – nausea or vomiting Gastrointestinal – other changes
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human – man
DOSE/DURATION :
8571 ug/kg
TOXIC EFFECTS :
Gastrointestinal – ulceration or bleeding from duodenum Gastrointestinal – nausea or vomiting Gastrointestinal – other changes
TYPE OF TEST :
LDLo – Lowest published lethal dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human – child
DOSE/DURATION :
250 mg/kg
TOXIC EFFECTS :
Behavioral – coma
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human – woman
DOSE/DURATION :
167 mg/kg
TOXIC EFFECTS :
Cardiac – EKG changes not diagnostic of specified effects Vascular – BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration – respiratory depression
TYPE OF TEST :
LDLo – Lowest published lethal dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human – man
DOSE/DURATION :
179 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 :
Oral
SPECIES OBSERVED :
Rodent – rat
DOSE/DURATION :
600 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 :
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 :
Intraperitoneal
SPECIES OBSERVED :
Rodent – mouse
DOSE/DURATION :
68 mg/kg
TOXIC EFFECTS :
Behavioral – convulsions or effect on seizure threshold
TYPE OF TEST :
LD50 – Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent – mouse
DOSE/DURATION :
200 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 – dog
DOSE/DURATION :
8 mg/kg
TOXIC EFFECTS :
Behavioral – somnolence (general depressed activity)
TYPE OF TEST :
LD50 – Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Bird – domestic
DOSE/DURATION :
64500 ug/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 :
8820 mg/kg/21W-C
TOXIC EFFECTS :
Cardiac – other changes Liver – hepatitis (hepatocellular necrosis), diffuse Related to Chronic Data – death
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent – rat
DOSE/DURATION :
840 mg/kg/21D-I
TOXIC EFFECTS :
Behavioral – food intake (animal) Kidney, Ureter, Bladder – urine volume decreased Nutritional and Gross Metabolic – weight loss or decreased weight gain
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent – rat
DOSE/DURATION :
400 mg/kg/10D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder – proteinuria Kidney, Ureter, Bladder – other changes in urine composition Biochemical – Enzyme inhibition, induction, or change in blood or tissue levels – phosphatases
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Ocular
SPECIES OBSERVED :
Rodent – rat
DOSE/DURATION :
72 ug/kg/12D-I
TOXIC EFFECTS :
Sense Organs and Special Senses (Eye) – corneal damage
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Mammal – dog
DOSE/DURATION :
280 mg/kg/14D-I
TOXIC EFFECTS :
Behavioral – tremor Related to Chronic Data – death
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Primate – monkey
DOSE/DURATION :
1 gm/kg/10D-I
TOXIC EFFECTS :
Liver – fatty liver degeneration 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
DOSE :
1200 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 :
550 mg/kg
SEX/DURATION :
female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive – Specific Developmental Abnormalities – eye/ear
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
750 mg/kg
SEX/DURATION :
female 9 day(s) after conception
TOXIC EFFECTS :
Reproductive – Effects on Embryo or Fetus – fetal death
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
80 mg/kg
SEX/DURATION :
female 20-21 day(s) after conception
TOXIC EFFECTS :
Reproductive – Specific Developmental Abnormalities – respiratory system Reproductive – Effects on Newborn – physical
TYPE OF TEST :
TDLo – Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
475 mg/kg
SEX/DURATION :
female 10-14 day(s) after conception
TOXIC EFFECTS :
Reproductive – Effects on Newborn – physical

MUTATION DATA

TYPE OF TEST :
Sister chromatid exchange
TEST SYSTEM :
Rodent – hamster Lung
DOSE/DURATION :
100 ug/L
REFERENCE :
CBTOE2 Cell Biology and Toxicology. (Princeton Scientific Pub., Inc., 301 N. Harrison St., CN 5279, Princeton, NJ 08540) V.1- 1984- Volume(issue)/page/year: 2,379,1986 *** REVIEWS *** TOXICOLOGY REVIEW INTEAG Internist. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1960- Volume(issue)/page/year: 15,7,1974 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES – National Occupational Exposure Survey (1983) NOES Hazard Code – X4486 No. of Facilities: 40 (estimated) No. of Industries: 2 No. of Occupations: 3 No. of Employees: 644 (estimated) No. of Female Employees: 238 (estimated)

 Safety Information

Symbol GHS07
GHS07
Signal Word Warning
Hazard Statements H302
Precautionary Statements P301 + P312 + P330
Personal Protective Equipment dust mask type N95 (US);Eyeshields;Gloves
Hazard Codes Xn:Harmful;
Risk Phrases R22
Safety Phrases S22-S24/25
RIDADR 1544
WGK Germany 3
RTECS VB2450000
Packaging Group III
Hazard Class 6.1(b)
HS Code 2933499090

 Precursor & DownStream

Precursor  0
DownStream  1

 Customs

HS Code 2933499090
Summary 2933499090. other compounds containing in the structure a quinoline or isoquinoline ring-system (whether or not hydrogenated), not further fused. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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 Synonyms

MFCD00069852
acide phosphorique – N-(7-chloroquinoléin-4-yl)-N,N-diéthylpentane-1,4-diamine (2:1)
Chloroquine phosphate
7-Chloro-4-[4-(diethylamino)-1-methylbutylamino]quinoline Diphosphate
EINECS 200-055-2
N-(7-chloroquinolin-4-yl)-N,N-diethylpentane-1,4-diamine bis(phosphate)
N4-(7-chloroquinolin-4-yl)-N1,N1-diethylpentane-1,4-diamine phosphate (1:2)
N-(7-Chloro-4-quinolinyl)-N,N-diethyl-1,4-pentanediamine phosphate (1:2)
N4-(7-Chloro-4-quinolyl)-N1,N1-diethyl-1,4-pentanediamine Diphosphate
Chloroquine diphosphate salt
7-Chloro-4-((4-(diethylamino)-1-methylbutyl)amino)quinoline phosphate (1:2)
Aralen phosphate
1,4-Pentanediamine, N-(7-chloro-4-quinolinyl)-N,N-diethyl-, phosphate (1:2)
1,4-pentanediamine, N4-(7-chloro-4-quinolinyl)-N1,N1-diethyl-, phosphate (1:2)
N-(7-Chloroquinolin-4-yl)-N,N-diethylpentane-1,4-diamine phosphate (1:2)
Chloroquine diphosphate
Imagon
Tresochin
Chloroquinediphosphate
Malaquin
Phosphorosäure–N-(7-chlorchinolin-4-yl)-N,N-diethylpentan-1,4-diamin(2:1)

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