METHYLCHLOROISOTHIAZOLINONE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C4H4ClNOS
Molecular Weight	149.599
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of METHYLCHLOROISOTHIAZOLINONE

Structure Search

SMILES

CN1SC(Cl)=CC1=O

InChI

InChIKey=DHNRXBZYEKSXIM-UHFFFAOYSA-N

InChI=1S/C4H4ClNOS/c1-6-4(7)2-3(5)8-6/h2H,1H3

HIDE SMILES / InChI

Molecular Formula	C4H4ClNOS
Molecular Weight	149.599
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.cosmeticsinfo.org/ingredient/methylisothiazolinone-and-methylchloroisothiazolinone
Curator's Comment: description was created based on several sources, including: DOI: 10.1007/978-3-642-55706-4_7 http://ec.europa.eu/consumers/sectors/cosmetics/files/pdf/mci_mi/mci_mi_pc_en.pdf Methylisothiazolinone/Methylchloroisothiazolinone (Kathon CG) Allergy: An Updated Review.

Methylchloroisothiazolinone is an active ingredient in many preservatives marketed under various brand names. It is effective against gram-positive and gram-negative bacteria, yeast, and fungi. Pure Methylchloroisothiazolinone is not commercially available. Kathon CG contains a mixture of Methylisothiazolinone (MI) and Methylchloroisothiazolinone (MCI) in ratio 3:1. Kathon was used in various rinse-off and leave-on formulations including hair products, shampoos, skin care products, bath products, eye and facial makeup, wet wipes and suntan products. The Commission envisages amending Annex V of the Cosmetics Regulation (EC) No. 1223/2009 to restrict the use of methylchloroisothiazolinone to rinse-off products, as suggested by the SCCS.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
aerobic respiration 4 Target ID: GO:0009060 Sources: http://www.ppchem.com/free/ppchem-01-2007-2.pdf	Inhibitor 8504
Alcohol dehydrogenase 6 Target ID: CHEMBL2096668 Sources: http://www.ppchem.com/free/ppchem-01-2007-2.pdf	Inhibitor 8504
ATP synthesis 1 Target ID: ATP synthesis Sources: http://www.ppchem.com/free/ppchem-01-2007-2.pdf	Inhibitor 8504
reactive oxygen species biosynthetic process 41 Target ID: GO:1903409 Sources: http://www.ppchem.com/free/ppchem-01-2007-2.pdf	Activator 1447

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic contact dermatitis 14 Sources: http://www.fda.gov/downloads/BiologicsBloodVaccines/Allergenics/UCM294327.pdf	Diagnostic		Approved 8583	TRUE Test Approved Use 5-chloro-2-methyl-4-isothiazolin-3-one (1.05% to 1.25% w/w) and 2-methyl-4-isothiazolin-3-one (0.25% to 0.40% w/w) in a 3:1 ratio at a concentration of 1.5% in aqueous magnesium salts are used to formulate patch #17

C_max

Value	Dose	Co-administered	Analyte	Population
282 μg/g EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28929222/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		N-METHYLMALONAMIC ACID urine	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28929222/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		N-METHYLMALONAMIC ACID urine	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1000 ppm single, topical Highest studied dose Dose: 1000 ppm Route: topical Route: single Dose: 1000 ppm Sources: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0536.1986.tb01166.x	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0536.1986.tb01166.x	Other AEs: Sensitization... Other AEs: Sensitization (12.5%) Sources: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0536.1986.tb01166.x

AEs

AE	Significance	Dose	Population
Sensitization	12.5%	1000 ppm single, topical Highest studied dose Dose: 1000 ppm Route: topical Route: single Dose: 1000 ppm Sources: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0536.1986.tb01166.x	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0536.1986.tb01166.x

PubMed

Title	Date	PubMed
Chemical allergens stimulate human epidermal keratinocytes to produce lymphangiogenic vascular endothelial growth factor.	2015-03-01	25617811
B cell increases and ex vivo IL-2 production as secondary endpoints for the detection of sensitizers in non-radioisotopic local lymph node assay using flow cytometry.	2012-03-25	22245253
The intra- and inter-laboratory reproducibility and predictivity of the KeratinoSens assay to predict skin sensitizers in vitro: results of a ring-study in five laboratories.	2011-04	21195160
Analysis of isothiazolinone biocides in paper for food packaging by ultra-high-performance liquid chromatography-tandem mass spectrometry.	2010-12	20960358
Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes.	2010-11-10	20713136
Prevalence and cause of methylisothiazolinone contact allergy.	2010-09	20690940
A new in vitro method for identifying chemical sensitizers combining peptide binding with ARE/EpRE-mediated gene expression in human skin cells.	2010-09	20491607
Methylchloroisothiazolinone / methylisothiazolinone and moist wipe dermatitis.	2010-05-15	20492831
Consumer exposure to biocides--identification of relevant sources and evaluation of possible health effects.	2010-02-03	20128903
Concomitant contact allergy to methylchloroisothiazolinone/methylisothiazolinone and formaldehyde-releasing preservatives.	2010-01	20136882
Mechanistic assessment of peptide reactivity assay to predict skin allergens with Kathon CG isothiazolinones.	2009-04	19444925
Expression of surface markers on the human monocytic leukaemia cell line, THP-1, as indicators for the sensitizing potential of chemicals.	2009-04	19338585
Role of intracellular calcium and S-glutathionylation in cell death induced by a mixture of isothiazolinones in HL60 cells.	2009-03	19118583
Methyl gallate.	2009-01-14	21581923
Alkalization of wall paint prevents airborne contact dermatitis in patients with sensitization to isothiazolinones.	2008-08	18759890
Suitability of macrophage inflammatory protein-1beta production by THP-1 cells in differentiating skin sensitizers from irritant chemicals.	2008-04	18353026
Airborne allergic contact dermatitis to methylchloroisothiazolinone/methylisothiazolinone in ironing water.	2008-03	18279170
Different regulation of T helper 1- and T helper 2-promoting cytokine signalling factors in human dendritic cells after exposure to protein versus contact allergens.	2008-01	18154619
Quantitative relationships between patch test reactivity and use test reactivity: an overview.	2008	18988092
Analysis of isothiazolinones in environmental waters by gas chromatography-mass spectrometry.	2007-09-14	17681349
Iron dependent degradation of an isothiazolone biocide (5-chloro-2-methyl-4-isothiazolin-3-one).	2007	17453731
Preservatives sensitivity in Israel: a 10-year overview (1995-2004).	2006-10	16958921
GSH depletion, protein S-glutathionylation and mitochondrial transmembrane potential hyperpolarization are early events in initiation of cell death induced by a mixture of isothiazolinones in HL60 cells.	2006-02	16458373
Patch testing with patients' own cosmetics and toiletries--results of the IVDK*, 1998-2002.	2005-10	16191021
Oxidative stress in mouse skin following application of contact allergenic 5-chloro-2-methyl-4-isothiazolin-3-one and oxazolone.	2005-03	15811043
From experiment to theory: molecular orbital parameters to interpret the skin sensitization potential of 5-chloro-2-methylisothiazol-3-one and 2-methylisothiazol-3-one.	2005-02	15720139
Effect of glutathione on the covalent binding of the 13C-labeled skin sensitizer 5-chloro-2-methylisothiazol-3-one to human serum albumin: identification of adducts by nuclear magnetic resonance, matrix-assisted laser desorption/ionization mass spectrometry, and nanoelectrospray tandem mass spectrometry.	2004-09	15377163
Covalent binding of the 13C-labeled skin sensitizers 5-chloro-2-methylisothiazol-3-one (MCI) and 2-methylisothiazol-3-one (MI) to a model peptide and glutathione.	2004-01-19	14698160
Contact sensitization to 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one in children.	2003-10	14996074
Co-existing sensitivity to metronidazole and isothiazolinone.	2003-09	12950340
Involvement of oxidative stress in apoptosis induced by a mixture of isothiazolinones in normal human keratinocytes.	2003-08	12880425
Studies of chemical selectivity of hapten, reactivity, and skin sensitization potency. 3. Synthesis and studies on the reactivity toward model nucleophiles of the 13C-labeled skin sensitizers, 5-chloro-2-methylisothiazol-3-one (MCI) and 2-methylisothiazol-3-one (MI).	2003-05	12755592
Coupling of contact sensitizers to thiol groups is a key event for the activation of monocytes and monocyte-derived dendritic cells.	2003-02	12542528
Audit of Finn Chamber patch test preparation.	2002-12	12581278
Elucidating changes in surface marker expression of dendritic cells following chemical allergen treatment.	2002-08-01	12183102
Monitoring levels of preservative sensitivity in Europe. A 10-year overview (1991-2000).	2002-04	12081698
In vitro induction of apoptosis vs. necrosis by widely used preservatives: 2-phenoxyethanol, a mixture of isothiazolinones, imidazolidinyl urea and 1,2-pentanediol.	2002-02-01	11853695

Patents

Sample Use Guides

In Vivo Use Guide

3 mcg of 5-chloro-2-methyl-4-isothiazolin-3-one (1.05% to 1.25% w/w) and 2-methyl-4-isothiazolin-3-one (0.25% to 0.40%w/w) in a 3:1 ratio per patch. Schedule patients to return approximately 48 hours after patch test application to have the panels removed.

Route of Administration: Topical

In Vitro Use Guide

5-Chloro-2-methyl-4-isothiazolin-3-one inhibited growth in all test strains of Salmonella typhimurium without activation. A statistically significant increase in the number of revertants in strain TA100 was observed without activation at concentrations of 0.20, 0.25 and 0.30 ug/plate and in 2 of the 3 trials at 0.10 ug/plate.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:10:28 GMT 2025` Edited by `admin` on `Mon Mar 31 18:10:28 GMT 2025`
Record UNII	DEL7T5QRPN
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METHYLCHLOROISOTHIAZOLINONE

Official Name

English

A 33

Preferred Name

English

5-CHLORO-2-METHYL-3-ISOTHIAZOLONE

Systematic Name

English

METHYLCHLOROISOTHIAZOLINONE [II]

Common Name

English

METHYLCHLOROISOTHIAZOLINONE [MART.]

Common Name

English

5-CHLOR-2-METHYL-4-ISOTHIAZOLIN-3-ONE

Common Name

English

A-33

Code

English

METHYLCHLOROISOTHIAZOLINONE [MI]

Common Name

English

3(2H)-ISOTHIAZOLONE, 5-CHLORO-2-METHYL-

Systematic Name

English

5-CHLORO-N-METHYLISOTHIAZOLONE

Systematic Name

English

Methylchloroisothiazolinone [WHO-DD]

Common Name

English

5-CHLORO-2-METHYL-2H-ISOTHIAZOL-3-ONE

Systematic Name

English

5-CHLORO-2-METHYL-ISOTHIAZOL-3-ONE

Systematic Name

English

5-CHLORO-2-METHYL-3(2H)-ISOTHIAZOLONE

Systematic Name

English

N-METHYL-5-CHLOROISOTHIAZOLONE

Systematic Name

English

N-METHYL-5-CHLOROISOTHIAZOLIN-3-ONE

Systematic Name

English

METHYLCHLOROISOTHIAZOLINONE [VANDF]

Common Name

English

HS 818

Code

English

NEOLONE 950

Brand Name

English

5-CHLORO-2-METHYLISOTHIAZOLIN-3-ONE

Systematic Name

English

5-CHLORO-2-METHYL-4-ISOTHIAZOLIN-3-ONE

Systematic Name

English

4-ISOTHIAZOLIN-3-ONE, 5-CHLORO-2-METHYL-

Systematic Name

English

5-CHLORO-N-METHYLISOTHIAZOLIN-3-ONE

Systematic Name

English

HS-818

Code

English

2-METHYL-5-CHLOROISOTHIAZOLIN-3-ONE

Systematic Name

English

2-METHYL-5-CHLORO-3-ISOTHIAZOLONE

Systematic Name

English

5-CHLORO-2-METHYL-3(2H)-ISOTHIAZOLINONE

Systematic Name

English

Classification Tree Code System Code

Food Contact Sustance Notif, (FCN No.)

FCN NO. 704