CARBON DISULFIDE

General Information

Mainterm	CARBON DISULFIDE
CAS Reg.No.(or other ID)	75-15-0
Regnum	175.105 177.2600

From www.fda.gov

Computed Descriptors

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2D Structure
CID	6348
IUPAC Name	methanedithione
InChI	InChI=1S/CS2/c2-1-3
InChI Key	QGJOPFRUJISHPQ-UHFFFAOYSA-N
Canonical SMILES	C(=S)=S
Molecular Formula	CS2
Wikipedia	carbon disulfide

From Pubchem

Computed Properties

Property Name	Property Value
Molecular Weight	76.131
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	0
Complexity	18.3
CACTVS Substructure Key Fingerprint	A A A D c Q A A A A B g A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A Q A A A A A A A A A A A A A A A A A A A A E A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area	64.2
Monoisotopic Mass	75.944
Exact Mass	75.944
XLogP3	None
XLogP3-AA	2.1
Compound Is Canonicalized	True
Formal Charge	0
Heavy Atom Count	3
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

From Pubchem

ADMET Predicted Profile --- Classification

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.9763
Human Intestinal Absorption	HIA+	0.9930
Caco-2 Permeability	Caco2+	0.7055
P-glycoprotein Substrate	Non-substrate	0.9109
P-glycoprotein Inhibitor	Non-inhibitor	0.9680
P-glycoprotein Inhibitor	Non-inhibitor	0.9910
Renal Organic Cation Transporter	Non-inhibitor	0.9265
Distribution
Subcellular localization	Lysosome	0.6314
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8380
CYP450 2D6 Substrate	Non-substrate	0.8379
CYP450 3A4 Substrate	Non-substrate	0.8255
CYP450 1A2 Inhibitor	Non-inhibitor	0.8221
CYP450 2C9 Inhibitor	Non-inhibitor	0.8716
CYP450 2D6 Inhibitor	Non-inhibitor	0.9677
CYP450 2C19 Inhibitor	Non-inhibitor	0.9081
CYP450 3A4 Inhibitor	Non-inhibitor	0.9628
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.7801
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9572
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9708
AMES Toxicity	Non AMES toxic	0.9133
Carcinogens	Carcinogens	0.6525
Fish Toxicity	High FHMT	0.5623
Tetrahymena Pyriformis Toxicity	High TPT	0.5910
Honey Bee Toxicity	High HBT	0.8826
Biodegradation	Not ready biodegradable	0.9562
Acute Oral Toxicity	III	0.8106
Carcinogenicity (Three-class)	Non-required	0.5038

From admetSAR

ADMET Predicted Profile --- Regression

Model	Value	Unit
Absorption
Aqueous solubility	-0.9546	LogS
Caco-2 Permeability	1.6659	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	1.8336	LD50, mol/kg
Fish Toxicity	1.7945	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.0258	pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of Exposure	Inhalation ; oral ; dermal ; eye contact
Mechanism of Toxicity	Carbon disulfide is a potent nerve toxin and also affect liver enzymes, particularly those related to lipid metabolism. The increases in serum cholesterol that are sometimes seen following carbon disulfide exposure may be a result of increased hepatic cholesterol synthesis. The primary target of carbon disulfide appears to be the nervous system. Neurophysiological and behavioral effects as well as pathomorphology of peripheral nervous system structures have been reported in humans. Moreover, carbon disulfide metabolites of the thiocarbamate type inhibit aldehyde anhydrase.
Metabolism	Nitrogenase reduces carbon disulfide and can also be inhibited by this toxin. Carbon disulfide binds (in the form of AL CS2) mainly to hemoglobin and to a small extent to other blood proteins, such as albumin and gamma-globulin. Carbon disulfide is bioactivated by cytochrome P-450 to an unstable oxygen intermediate. The intermediate may either spontaneously degrade to atomic sulfur and carbonyl sulfide or hydrolyze to form atomic sulfur and monothiocarbonate. The atomic sulfur generated in these reactions may either covalently bind to macromolecules or be oxidized to products such as sulfate. The carbonyl sulfide formed may be converted to monothiocarbonate by carbonic anhydrase. Monothiocarbonate may further spontaneously degrade, regenerating carbonyl sulfide or forming carbon dioxide and sulfide bisulfide ion (HS-). The HS- formed can subsequently be oxidized to sulfate or other nonvolatile metabolites. Dithiocarbamates are the products of the reaction of carbon disulfide with amino acids. Most of the carbon disulfude absorbed is metabolized. Small traces of unchanged can be found in the urine. Carbon disulfide or carbonyl sulfide can conjugate with endogenous glutathione to yield thiazolidine-2-thione-4-carboxylic acid and 2-oxythiazolidine-4-carboxylic acid, respectively. Carbonic anhydrase 2 mediates the metabolism of carbon disulfide.
Toxicity Values	LD50: 3020 mg/kg/day (Oral, Mouse)
Lethal Dose	None
Carcinogenicity (IARC Classification)	No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk Level	Chronic Inhalation: 0.3 ppm Acute Oral: 0.01 mg/kg/day
Health Effects	Following inhalation, subtle and transient changes in pulmonary function can be manifested as reduced vital capacity and decreased partial pressure of arterial oxygen. Patients can developed normochromic and normocytic anemia, eosinopenia, and an increase in reticulocyte cell numbers after oral exposure . Carbon disulfide poisoning can result in central nervous system depression, coma, respiratory paralysis, and death. It also may accelerate coronary artery disease. Peripheral neuropathies, cranial nerve dysfunction, and neuropsychiatric changes are present in over 70% of chronic carbon sulfide victims. (L592)
Treatment	Following oral exposure, administer charcoal as a slurry (240 mL water/30 g charcoal). Consider gastric lavage after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Intravenous urea (0.5 to 1.5 g/kg) has been recommended to inactivate free carbon disulfide in the blood. The efficacy of this treatment is unknown. Following inhalation exposure, move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. If the exposure occurred through eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If the exposure occurred through dermal contact, remove contaminated clothing and wash exposed area thoroughly with soap and water.
Reference	Sams C, Loizou GD, Cocker J, Lennard MS: Metabolism of ethylbenzene by human liver microsomes and recombinant human cytochrome P450s (CYP). Toxicol Lett. 2004 Mar 7;147(3):253-60.[15104117 ] Haritos VS, Dojchinov G: Carbonic anhydrase metabolism is a key factor in the toxicity of CO2 and COS but not CS2 toward the flour beetle Tribolium castaneum [Coleoptera: Tenebrionidae]. Comp Biochem Physiol C Toxicol Pharmacol. 2005 Jan;140(1):139-47.[15792633 ] Masuda Y, Yasoshima M, Nakayama N: Early, selective and reversible suppression of cytochrome P-450-dependent monooxygenase of liver microsomes following the administration of low doses of carbon disulfide in mice. Biochem Pharmacol. 1986 Nov 15;35(22):3941-7.[3778518 ] Ryle MJ, Lee HI, Seefeldt LC, Hoffman BM: Nitrogenase reduction of carbon disulfide: freeze-quench EPR and ENDOR evidence for three sequential intermediates with cluster-bound carbon moieties. Biochemistry. 2000 Feb 8;39(5):1114-9.[10653657 ] Seefeldt LC, Rasche ME, Ensign SA: Carbonyl sulfide and carbon dioxide as new substrates, and carbon disulfide as a new inhibitor, of nitrogenase. Biochemistry. 1995 Apr 25;34(16):5382-9.[7727396 ] Lam CW, DiStefano V: Characterization of carbon disulfide binding in blood and to other biological substances. Toxicol Appl Pharmacol. 1986 Nov;86(2):235-42.[3787622 ] Schreiner E, Freundt KJ: Behaviour of epoxide hydrolase, glutathione S-transferase, alcohol dehydrogenase, and aldehyde dehydrogenase, respectively, under the influence of carbon disulfide studies with rats in vivo and in vitro. G Ital Med Lav. 1984 May-Jul;6(3-4):131-3.[6242047 ]

From T3DB

Taxonomic Classification

Kingdom	Inorganic compounds
Superclass	Homogeneous non-metal compounds
Class	Other non-metal organides
Subclass	Other non-metal sulfides
Intermediate Tree Nodes	Not available
Direct Parent	Other non-metal sulfides
Alternative Parents	Inorganic sulfides
Molecular Framework	Not available
Substituents	Other non-metal sulfide - Inorganic sulfide
Description	This compound belongs to the class of inorganic compounds known as other non-metal sulfides. These are inorganic compounds containing a sulfur atom of an oxidation state of -2, in which the heaviest atom bonded to the oxygen belongs to the class of other non-metals.

From ClassyFire

Targets

Target Details

Cytochrome P450 1A1

General Function:: Vitamin d 24-hydroxylase activity
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:: CYP1A1
Uniprot ID:: P04798
Molecular Weight:: 58164.815 Da

References

Dalvi PS, Wilder-Kofie T, Mares B, Dalvi RR, Billups LH. Toxicologic implications of the metabolism of thiram, dimethyldithiocarbamate and carbon disulfide mediated by hepatic cytochrome P450 isozymes in rats. Pesticide Biochemistry and Physiology Oct 2002;74(2):85-90. [16829625 ]

Target Details

Cytochrome P450 2E1

General Function:: Steroid hydroxylase activity
Specific Function:: Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:: CYP2E1
Uniprot ID:: P05181
Molecular Weight:: 56848.42 Da

References

Dalvi PS, Wilder-Kofie T, Mares B, Dalvi RR, Billups LH. Toxicologic implications of the metabolism of thiram, dimethyldithiocarbamate and carbon disulfide mediated by hepatic cytochrome P450 isozymes in rats. Pesticide Biochemistry and Physiology Oct 2002;74(2):85-90. [16829625 ]

Target Details

Dopamine beta-hydroxylase

General Function:: L-ascorbic acid binding
Specific Function:: Conversion of dopamine to noradrenaline.
Gene Name:: DBH
Uniprot ID:: P09172
Molecular Weight:: 69064.45 Da

References

McKenna MJ, DiStefano V: Carbon disulfide. II. A proposed mechanism for the action of carbon disulfide on dopamine beta-hydroxylase. J Pharmacol Exp Ther. 1977 Aug;202(2):253-66. [886465 ]

From T3DB