Chlorpyrifos Oxon

Names

[ Name ]:
Chlorpyrifos Oxon

[Synonym ]:
Chlorpyrifos Oxon

Biological Activity

[Description]:

Chlorpyrifos-oxon, an active metabolite of Chlorpyrifos, is a potent phosphorylating agent that potently inhibits AChE. Chlorpyrifos-oxon can induce cross-linking between subunits of tubulin and disrupt microtubule function[1][2][3][4].

[Related Catalog]:

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> AChE

[In Vitro]

Treatment of tubulin with 1.5 mM Chlorpyrifos-oxon (CPO) leads to protein aggregation. However, even at 1.5 μM Chlorpyrifos-oxon cross-linked trimers are apparent. Chlorpyrifos-oxon promotes isopeptide bond cross-linking of tubulin monomers to make multimers[2]. In PC12 cells in culture, 24 hours of exposure to Chlorpyrifos at a concentration 10-fold below the concentration that inhibits AChE activity (3.0 μM) impaired neurite outgrowth while Chlorpyrifos-oxon inhibits neurite outgrowth at 1.0 nM[3].

[In Vivo]

Chlorpyrifos-oxon (CPO) is rapidly detoxified by human liver microsomes via CYP-dependent deethylation and dearylation, and by glutathione-S-transferase. In addition, reactions with A-esterases such as paraoxonase 1 (PON 1) or B-esterases such as carboxylesterase and butyrylcholinesterase (BChE) in the liver may rapidly degrade or scavenge Chlorpyrifos-oxon[1]. Chlorpyrifos-oxon (3 mg/kg, ip; once; wild-type mice) treatment shows the dimensions of microtubules from Chlorpyrifos-oxon-treated mice are about 60% of those from control mice. The microtubules from mice exposed to Chlorpyrifos-oxon have covalently modified amino acids and abnormal structure, suggesting disruption of microtubule function[4].

[References]

[1]. Florian Eyer, et al. Extreme variability in the formation of chlorpyrifos oxon (CPO) in patients poisoned by chlorpyrifos (CPF). Biochem Pharmacol. 2009 Sep 1;78(5):531-7.

[2]. Lawrence M Schopfer, et al. Chlorpyrifos oxon promotes tubulin aggregation via isopeptide cross-linking between diethoxyphospho-Lys and Glu or Asp: Implications for neurotoxicity. J Biol Chem. 2018 Aug 31;293(35):13566-13577.

[3]. Jie Gao, et al. Chlorpyrifos and chlorpyrifos oxon impair the transport of membrane bound organelles in rat cortical axons. Neurotoxicology. 2017 Sep;62:111-123.

[4]. Wei Jiang, et al. Mice treated with chlorpyrifos or chlorpyrifos oxon have organophosphorylated tubulin in the brain and disrupted microtubule structures, suggesting a role for tubulin in neurotoxicity associated with exposure to organophosphorus agents. Toxicol Sci. 2010 May;115(1):183-93.

Chemical & Physical Properties

[ Density]:
1.461g/cm3

[ Boiling Point ]:
357.8ºC at 760mmHg

[ Molecular Formula ]:
C₉H₁₁Cl₃NO₄P

[ Molecular Weight ]:
334.52100

[ Flash Point ]:
170.2ºC

[ Exact Mass ]:
332.94900

[ PSA ]:
67.46000

[ LogP ]:
4.60170

[ Index of Refraction ]:
1.523

[ Storage condition ]:
0-6°C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TC2370100

CHEMICAL NAME :: Phosphoric acid, diethyl 3,5,6-trichloro-2-pyridyl ester

CAS REGISTRY NUMBER :: 5598-15-2

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C9-H11-Cl3-N-O4-P

MOLECULAR WEIGHT :: 334.53

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 135 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: PB85-143766

Safety Information

[ Hazard Codes ]:
T+

[ RIDADR ]:
UN 2783

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

Precursor & DownStream

Precursor

DownStream

Related Compounds

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