ISOTHIAZOLINONES
ISOTHIAZOLINONES
Isothiazolinones
CAS No. 26172-55-4, 2682-20-4 Molecular Weight: 115.16
Structural Formula:HCCNHCCH3S12345HCCNCC3 S12345ClOO
2-methyl-4-thiazoline-3-ketone(MI) 5-chloro- methyl-4-thiazoline-3-ketone(CMI)
Properties:
Isothiazolinones is composed of 5-chloro-2-methyl-4-thiazoline-3-ketone (CMI) and 2-methyl-4-thiazoline-3-ketone (MI). The bactericidal effect of Isothiazolinones is carried out through breaking the bond between bacteria and algae protein. When contacted with microbes, Isothiazolinones can quickly inhibit their growth, thus leading to death of these microbes. Isothiazolinones has strong inhibition and biocidal effects on ordinary bacteria, fungi and alga, and has many advantages such as high biocidal efficiency, good degradation, no residual, safety in operation, good compatibleness, good stabilization, low cost in operation.
Isothiazolinones can mix with chlorine and most cation, anion, and non-ionic surfactants. When used at high dosage, its biosludge stripping effect is excellent.
Isothiazolinones is a kind of fungicidal with properties of broad spectrum, high efficiency, low toxicity and non-oxidative, it is the ideal biocidal in industrial circulating cool water system and in wastewater treatment in oilfield, papermaking, pesticide, cutting oil, leather, detergent and cosmetics etc..
Isothiazolinone (sometimes isothiazolone) is a organic compound with the formula (CH)2SN(H)CO
Isothiazolone itself is of limited interest, but several of its derivatives are widely used preservatives and antimicrobials
The antimicrobial activity of isothiazolinones is attributed to their ability to inhibit life-sustaining enzymes. Specifically those enzymes with thiols at their active sites. It is established that isothiazolinones form mixed disulfides upon treatment with such species.
Isothiazolinones find application in the preservation of high pH household and industrial and institutional (I & I) cleaning formulations, as well as personal care and cosmetic materials.
2-Methyl-4-isothiazolin-3-one (MIT), finds application in domestic and I & I cleaners, whereas the same product in combination with 5-chloro-2-methyl-4-isothiazolin-3-one (CIT) is an established preservative in personal care and cosmetic products.
1,2-Benzisothiazolin-3-one (BIT) (Figure F.2.21) also has biocidal activity but is more commonly used in metal working/cutting oil applications.
The combination of CIT and MIT is one of the most cost-effective biocides for industrial preservation in the wet state. CIT has by far the greater biocidal efficacy but is by far the least stable of the two components. Although MIT alone has relatively low antimicrobial performance, it has been discovered that it has truly synergistic activity in combination with BIT. For example, individual minimum inhibitory concentration (MIC) for BIT and MIT against Pseudomonas aeruginosa are 150 and 30 ppm respectively, whereas for MIT/BIT in combination, it is 20 ppm. This is borne out for many other organisms.
The maximum use level of MIT/CIT in personal care and cosmetic products is 15 ppm as it is a skin sensitiser and hence mainly used in rinse-off products. Its stability is also reduced above pH 8. However, it is extremely effective at very low concentrations, has a broad spectrum of activity, is water soluble and compatible with nonionic surfactants.
Recent results have shown that 2-methyl-4-isothiazolin-3-one (MIT) alone is stable and effective against many bacteria and fungi in a range of household and I & I products
Usage:
When used as sludge stripper for grade II, the dosage of 150-300mg/L is preferred, when used as boicide, the dosage of 80-100mg/L is preferred, and charges every 3-7 days. No used together with oxidative fungicidal such as chlorine, and no used in cooling water system containing sulfur. When used together with quaternary amine, the effect will be better. When used as industrial fungicide, the dosage of 0.05-0.4% is preferred.
Package and Storage: 25kg in plastic barrel, or confirmed by clients. Storage for ten months in room shady and dry place.
Applications
The principal isothiazolones are:
Methylisothiazolinone (MIT, MI)
Chloromethylisothiazolinone (CMIT, CMI, MCI)
Benzisothiazolinone (BIT)
Octylisothiazolinone (OIT, OI)
Dichlorooctylisothiazolinone (DCOIT, DCOI)
Butylbenzisothiazolinone (BBIT)
These compounds all exhibit antimicrobial properties. They are used to control bacteria, fungi, and algae in cooling water systems, fuel storage tanks, pulp and paper mill water systems, oil extraction systems, wood preservation, and some paints. They are antifouling agents. They are frequently used in shampoos and other hair care products.[4][5]
Chloromethylisothiazolinone (CMIT) and 2-methyl-4-isothiazolin-3-one (methylisothiazolinone or MIT) are popular derivatives.
A 3:1 mixture of CMIT:MIT is sold as Kathon. Kathon is supplied as a concentrated stock solution containing from 1.5–15% of CMIT/MIT.
For applications the recommended use level is from 6 ppm to 75 ppm active isothiazolones.
4,5-Dichloro-2-n-octyl-4-isothiazolino-3-one (DCOI or Sea-Nine 211) is used especially as an antifouling agent, i.e. paint for ship hulls to prevent the formation of barnacles, etc.
Allergic contact dermatitis
Methylisothiazolinone is used commonly in products in conjunction with methylchloroisothiazolinone, a mixture sold under the registered trade name Kathon CG.
A common indication of sensitivity to Kathon CG is allergic contact dermatitis.
Sensitization to this family of preservatives was observed as early as the late 1980s.
The use of isothiazolinone-based preservatives has resulted in many incidences of contact allergy.
In 2013 the substance was declared the 2013 Contact Allergen of the Year by the American Contact Dermatitis Society.
Isothiazolinone mix includes the compounds 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one.
They are used together as a preservative in cosmetics and commercial household products such as shampoos, cleaners and washing materials.
It also has wide industrial uses.
Isothiazolinone mix is more commonly known as the preservative product with the commercial name Kathon.
Testing should also include methylisothiazolinone (MI), a related allergen that has caused an epidemic of contact allergic dermatitis in people using moist wipes and other products containing MI.
Isothiazolinones are used in cosmetic and as chemical additives for occupational and industrial usage due to their bacteriostatic and fungiostatic activity.
Despite their effectiveness as biocides, isothiazolinones are strong sensitizers, producing skin irritations and allergies and may pose ecotoxicological hazards.
Therefore, their use is restricted by EU legislation.
Considering the relevance and importance of isothiazolinone biocides, the present review describes the state-of-the-art knowledge regarding their synthesis, antibacterial components, toxicity (including structure–activity–toxicity relationships) outlines, and (photo)chemical stability.
Due to the increasing prevalence and impact of isothiazolinones in consumer’s health, analytical methods for the identification and determination of this type of biocides were also discussed.
Keywords: biocides, isothiazoles, isothiazolinones, chemistry, biological/toxicity relationships, stability, analysis
Isothiazol-3-ones are known for their remarkable antifungal and antibacterial properties, being extensively used as biocides in a variety of industrial water treatment applications for the control of microbial growth and biofouling.
They have also been recommended as preservatives to prevent fungal growth in a wide range of manufactured goods, such as emulsion paints, wood varnishes, adhesives, and natural and artificial leather.
The isothiazolinones most commonly found in commercial applications, alone or in combination, are methylisothiazolinone (MI), methylchloroisothiazolinone (MCI), benzisothiazolinone (BIT), octylisothiazolione (OIT), and dichlorocthylisothiazolinone (DCOIT).
Methylisothiazolinone is commonly used in wastewater treatment processes, cosmetics, paints, and detergents, and in combination with MCI (in proportions of 3:1) as an active ingredient of the commercial biocide, Kathon.
Although BIT and OIT are forbidden to be used in cosmetics, they are usually applied in cleaning and leather products, respectively, and as antifouling coating agents.
DCOIT, the biocidal ingredient in SeaNine 211, is a widely used antifouling agent to deter the undesirable biofouling phenomenon
Although there has been an increased use of isothiazolinones over the last years, concerns related to their inherent sensitization potential and allergic contact dermatitis, frequently observed both in consumers as well as workers in various industries, have been reported.
Moreover, cross-reactivity between different isothiazolinones has been demonstrated in animal assays and broadens the potential consequences of becoming sensitized to this type of compound
Isothiazolinone derivatives MI, MCI, BIT, OIT, and DCOIT are powerful biocides that are used as preservatives in a wide range of daily life products, such as detergents, paints, and cosmetic products. These compounds were described to be able to diffuse across the bacterial cell membrane and the cell wall of fungi.
In the intracellular media, the electron-deficient sulfur of the N–S bond of these compounds can react with the nucleophilic groups of the cellular components, such as the thiols from cysteines of proteins active sites blocking their enzymatic activity and ultimately causing cellular death.
Indeed, as demonstrated by Collier et al., MI, MCI and BIT are able to readily react with thiol-containing compounds, such as glutathione (GSH) and cysteine, to form disulfide derivatives and promote a series of reactions that impair key cellular functions, causing cellular growth inhibition in a few minutes and cellular death in few hours.
The antibacterial and antifungal activity of isothiazolinones is highly valued by a number of industries.
Therefore, over the years, several reports have been prepared illustrating their biocidal activity against a wide spectrum of industrial biological contaminants.
For instance, Collier et al. evaluated the biocidal activity of MI, MCI, and BIT against Schizosacchurornyces pombe and Escherichia coli.
In this study, MI showed the highest minimum growth inhibitory concentration (MIC) values, 245 μg/mL and 41 μg/mL for S. pombe and E. coli, respectively.
On the other hand, MCI displayed the lowest MIC values of the tested compounds, 2.6 μg/mL and 0.5 μg/mL for S. pombe and E. coli, respectively.
These results highlighted that the presence of the chlorine in the double bond of the isothiazolinone ring improves the compound’s biocidal activity.
In 1993, Green compared the efficacy of BIT and a commercial formulation containing a mixture of MCI:MI (4:1) against an autofluorescent species of Legionella bozemanii.
The biocide containing the mixture of MCI:MI was capable of inhibiting Legionella film formation below the assay detection levels at concentrations as low as 50 ppm of formulation, whereas BIT needed concentrations above 200 ppm to present a similar effect.
Furthermore, the content of MCI (% w/v) in the MCI:MI formulation was much lower than the amount of active compound on the commercial BIT formulation.
Hence, the overall results of this study revealed a higher potency of MCI against Legionella.
In a recent study, Rushton et al. demonstrated that BIT and a mixture of MI:MCI (3:1) displayed a bactericidal activity against 82 out of a panel 83 strains of bacteria from Burkholderia cepacia complex, which are well-known industrial contaminants.
Two independent studies compared the biocide activity of MI, MCI, OIT, DCOIT, and a mixture of MCI/MI against Aspergillus niger and Saccharomyces cerevisiae.
The highest MIC and minimum biocidal concentration (MBC) values for both fungi were disclosed after MI treatment.
On the other hand, all the other biocides showed a high inhibitory capacity with MIC and MBC values below 1 mg/L against both fungi.
Importantly, the authors observed that the potency of MCI, OIT, DCOIT, and of the MCI/MI mixture was nearly identical.
In summary, the biocidal activity of the reviewed isothiazolinones can be represented as MCI > OIT ≈ DCOIT > BIT > MI, and these results are paralleled by the cytotoxicity suggested for these compounds.
As a consequence, despite their potency, the EU has adopted a strict regulation in order to balance the risks and benefits for the workers manipulating these biocides and for the final consumers of the industrial products preserved with these compounds.
However, under the light of the most recent toxicological data, it is expected that the EU could adopt a stricter regulation on the use of isothiazolinone biocides during industrial processes and suggest the replacement of the most toxic biocides for others with similar potency, but with a superior safety profile.
The antimicrobial profile of isothiazolinones makes them highly efficient biocides, even at low concentrations.
However, despite its effectiveness, some of them are strong sensitizers, producing skin irritation and allergies, and they could pose ecotoxicological risks.
Consequently, its use has been restricted by EU legislation to limited concentrations depending on the product type to be preserved.
In order to guarantee consumers’ health and ensure compliance to existing regulations, reliable methodologies must be used to identify and quantify this type of biocides.
Isothiazolinones are used in cosmetic and chemical substances for occupational use and possess bacteriostatic and fungiostatic activity. Isothiazolinones are potent contact allergens. The use of the isothiazolinone methylchloroisothiazolinone (MCI) in 3:1 combination with methylisothiazolinone (MI) (MCI/MI) resulted in the 1980s in high prevalence rates of contact allergy to MCI/MI across the EU. This rapid increase in new cases of MCI/MI contact allergy instigated a restriction of MCI/MI to 15 ppm that subsequently resulted in decreasing prevalence rates of contact allergy to MCI/MI in the EU. Later, around the millennium, MI was introduced as a single preservative in chemical substances for occupational use, and in 2005 and onward, MI was introduced in cosmetic products as a single preservative. The use of MI has resulted in an unprecedented steep increase in new cases of contact allergy to MI on the European continent, the US, Asia, and Australia. In many countries, the prevalence rates of MI exceed 7–10%. These two epidemics have mainly been driven by use of MCI/MI and MI in cosmetic products, but both are as well important allergens in the work environment. Occupations at special risk for MCI/MI or MI sensitization are painters, blacksmiths, machine operators, cosmetologists, and tile setters.
Other isothiazolinones, e.g., benzisothiazolinone (BIT) and octylisothiazolione (OIT), are only used in industrial products and non-cosmetic consumer products such as paints and leather products and also pose a problem in special occupations.
Keywords
Methylisothiazolinone Benzisothiazolinone Octylisothiazolinone Risk occupations
Isothiazolinones have been used since the 1970s and are preservatives that possess bacteriostatic and fungiostatic activity.
The extensive use of a mixture of isothiazolinones (methylchloroisothiazolinone in fixed 3:1 combination with methylisothiazolinone; MCI/MI; Kathon™ CG) in cosmetic products resulted in the 1980s in a rapid increase of new cases of contact allergy to this mixture. Later the use and maximum concentration of MCI/MI was restricted due to its tendency to cause contact allergy.
The use of MI as a stand-alone preservative was introduced in industrial products around the millennium and soon thereafter in cosmetic products.
The use of MI, primarily in cosmetic products, has resulted in an unprecedented rapid increase in new cases of contact allergy to MI that has manifested as allergic contact dermatitis, primarily affecting the face and hands.
The European Commission (EC) has restricted the use of MI to 15 ppm in rinse-off cosmetic products as of 2018, and as of February 2017 MI has been totally banned in leave-on cosmetic products.
MI and MCI/MI are important allergens in the work environment. Occupations at special risk are painters, blacksmiths, machine operators, cosmetologists, and tile setters.
Occupational exposures associated with MI contact allergy are mostly cosmetic products such as moisturizers, liquid soaps, and wet wipes used at the workplace followed by cleansing agents, water-based paints, cutting oils, and glues and lacquers.
Other isothiazolinones (e.g., BIT and OIT) are not permitted in cosmetic products but may be used in industrial products. The most frequent products are paints, cutting oils, and leather products.
MI, along with other isothiazolinones, is added to water-based paint in relatively high concentrations, and MI may evaporate from newly painted rooms that may result in flare-ups of airborne allergic contact dermatitis.
Description
Isothiazolinone is a heterocyclic chemical compound related to isothiazole. Isothiazolinone is an antimicrobial preservative that is often used to control fungi, bacteria, and algae. Since water-containing solutions are the breeding grounds for bacteria, isothiazolinone can easily be used in such solutions.
Applications
Although isothiazolinones have no direct applications, their derivatives such as 5-chloro-2-methyl-4-isothiazolin-3-on and 2-methyl-4-isothiazolin-3 which are used together as preservatives in commercial households and cosmetics products, for instance, cleaners, shampoos, and washing materials. Notably, various products that use isothiazolinones are in the market, including shampoo, hand sanitizer, and lotions. Isothiazolinones is used in these products as an inhibitor of microbial activity that could lead to the product spoiling before the expected expiration date.
Safety Information
The recommended use of isothiazolinone products by the manufacturers used as wrinkle releaser is not harmful. However, allergy to skin is one of the most reported issue with isothiazolinone.
Description
Methy1chloro-isothiazolinone (MCI) is contained, along with methylisothiazolinone (MI), in Kathon cosmetic grade (CG) and MCI/MI. It is irritant and sensitizer.
Chemical Properties
Liquid
Uses
Isocil(R) MW-14 is a high performance biocide for preserving metal working fluids, hydraulic fluids, polymer emulsions, pigment dispersions. Suggested applications: preservative concentrate. Very low level.
Uses
Isocil(R) PC is a cost-effective antimicrobial for personal care formulations. Suggested applications: personal care preservative.
Uses
Isocil(R) RW is a high performance industrial microbiocide for use in recirculating water cooling towers, wood, mold and mildew control, pulp and paper mills, air washer systems. Suggested applications: Industrial water treatment. Very low use levels.
Uses
A isothiazolidin-3-one derivative as antimicrobial. It was tested for inhibition of PCAF activity. 5-Chloroisothiazolinones showed the most potent inhibition of PCAF.
Definition
ChEBI: A 1,2-thiazole that is 4-isothiazolin-3-one bearing a methyl group on the nitrogen atom and a chlorine at C-5. It is a powerful biocide and preservative and is the major active ingredient in the commercial product Kathon
• 4-Isothiazolin-3-one,5-chloro-2-methyl-
• 5-chloro-2-methyl-3(2h)-isothiazolon
• 5-chloro-2-methyl-4-isothiazolin-3-on
• Isothiazolinone
• 5-Chloro-2-methyl-4-isothiazolinone
• 5-CHLORIDE-2-METHYL-4-ISOTHIAZOLINE-3-KETONE
• 5-CHLORO-2-METHYL-4-ISOTHIAZOLIN-3-ONE (CMI)
• 5-CHLORO-2-METHYL-3(2H)-ISOTHIAZOLONE MIXED WITH 2-METHYL-3(2H)ISOTHIAZOLONE
• Methychloroisothiazolinone/Methylisothiazolinone
• 5-Chloro-2-Methyl-3(2H)-IsothiazoneMixedWith2-Methyl-3(2H)-Isothiazolone
• 5-Chloro-2-Methyl-3(2H)-Isothiazone
• 5-CHLORO-2-METHYL-4-ISOTHIAZOLIN-3-ONE (CMIT)
• Chloromethylisothiazolinone
• Chloromethylisothiazolone
• CMI
• CMIT
• Danisol-K
• MCI
• Methylchloroisothiazolone
• 5-Chloro-2-methyl-Isothiazolin-3-one/ 2-Methyl-Isothiazolin-3-one(CMIT/MIT)
• 5-CHLORO-2-METHYL-3(2H)-ISOTHIAZOLE
• METHYLCHLOROISOTHIAZOLINONE/METHYLISOTHIAZOLINONE
• 5-CHLORO-2-METHYL-ISOTHIAZOLIN-3(2H)-ONE
• 5-CHLORO-2-METHYLISOTHIAZOLINONE
• 5-CHLORO-2-METHYL-2,3-DIHYDROISOTHIAZOL-3-ONE
• METHYL/CHLOROMETHYLISOTHIAZOLINONE
• 2-METHYL-5-CHLOROISOTHIAZOLIN-3-ONE
• 5-CHLORO-2-METHYLISOTHIAZOLIN-3-ONE
• KATHON886F
• KATHONFP
• CHLOROMETHYLISOTHIAZOLINE
• METHYL(CHLORO)ISOTHIAZOLINONEMIXTURE
• KATHON886MW
• KATHONLX
• CHLORMETHYLISOTHIAZOLINONE
• CMIT (5 chloro 2 Methyl 2H isothiazol-3-one
• Isothiazolinones(CMI/MI)
• 3(2H)-Isothiazolone, 5-chloro-2-methyl-
• 3(2H)-Isothiazolone, 5-chloro-2-methyl-, mixt. with 2-methyl-3(2H)-isothiazolone
• CMIT/MIT MIXTURE
• Isothiazolinones
• CMIT/MIT
• 2-METHYL-5-CHLORO-4-ISO-THIAZOLINE-3-ONE
• 5-Chloro-2-Methyl-4-isothiazolin-3-one, >14% in water.
• CMIT/MIT-14
• 5-CHLORO-2-METHYL-4-ISOTHIAZOLIN-3-ONE (ACTIVE INGREDIENT >14%, CMI/MI 2.5 – 4.0)
• ANTI-IDAS(N-TERMINAL) antibody produced in rabbit
• IDAS
• Multicilin
• Protein Idas
• 5-cloro-2-methyl-4-isothiazolin-3-one/2-methyl-2h-isothiazol-3-one
• Isothiazolinones Solution,100ppm
• 5-Chloro-2-methyl-3-isothiazolone – Active Ingredient >14%, CMI/MI 2.5 – 4.0
• CMIT/MIT-2.5 CG
• Methyl chloroisothiazalinone
• Kathon.cmit/mit
• 5-chloro-2-methyl-isothiazolylthione-3
• kathoncg5243
Isothiazoilinone has proven effectiveness against a number of microorganisms such as fungi, algae and bacteria. SANITIZED offers a high quality, innovative range of products with various isothiazolinone active ingredients for various textile and polymer applications.
These products offer highly effective, durable protection of the materials against fungal, algal and bacterial infestation and prevent microbial related discolorations (pink stain).
Fields of application are mattresses, filters, tents and carpets.
Benzisothiazolinone (BIT)
Active ingredient: 1,2-Benzisothiazol-3(2H)-one (BIT)
Octylisothiazolinone (OIT)
Active ingredient: 2-Octyl-2H-isothiazol-3-one (OIT)
Butylbenzisothiazolinone (BBIT)
Active ingredient: 1, 2-benzisothiazolin-3-one, 2-butyl (BBIT)
Benefits
Broad spectrum of efficacy
Outstanding durability and effectiveness
Continuous material protection
Readily combined with many textile effects
Ease of application
Isothiazolinone consists of 5-chloro-2-methyl-4-thiazoline-3-ketone (CMI) and 2-methyl-4-thiazoline-3-ketone (MI).
The actual bactericidal effect of isothiazolinone is carried out by means of breaking the bond between bacterias and also algae proteins.
The moment approached together with microbes, CMIT/MIT can quickly prevent their growth.
Therefore, it results in the actual death of those microbes.
Isothiazolinone features powerful inhibition and biocidal effects on regular microorganisms, fungi, and also alga. And it has lots of advantages.
For example high biocidal efficiency, excellent degradation, zero residual, safety in operation, great compatibleness, superior stabilization, and affordable.
Isothiazolinone (CMIT/MIT) is able to combine together with chlorine and most cation, anion, and non-ionic surfactants. When applied with a large dosage, its biosludge stripping effect is fantastic.
CMIT/MIT is a type of fungicidal along with many properties. Such as broad-spectrum, high efficiency, low toxicity, and non-oxidative.
Isothiazolinone may be the best biocidal in the industrial circulating cool water system. And also in wastewater treatment in the oilfield, papermaking, pesticide, cutting oil, leather, detergent, and cosmetics, etc..