PRODUCTS

NIPACIDE CI 15

Nipacide CI 15 is an in-can biocide based on CMIT/MIT.
Nipacide CI 15 is a water based biocide, developed for the complete in-can protection of water based products including water based / Latex/PVA adhesives, PVA / acrylic polymer emulsions, water based decorative paints, printing inks, metal working fluids and construction admixtures.

CAS No. : 55965-84-9
EC No. : 696-206-9

Synonyms:
CMIT/MIT; nipasit cı 15; nipasid ci 15; nipacide ci 15; nipacide ci15; Latex; PVA adhesives; PVA / acrylic polymer emulsions; Aqueous solution of 5-Chlor-methylisothiazolin-3-one and 2-Methylisothiazolin-3-one; CMIT; MIT; CMIT MIT; Mergal K14; CMIT/MIT; 5-chloro-2-methyl-2h-isothiazolin-3-one/2-methyl-2h-isothiazol-3-one; Methylisothiazolinone; Liquid Industrial Microbiocide; Isothiazolin-3-one; 3(2H)-Isothiazolone, isothiazolin; Mergal A25; 83542-80-7; 3(2H)-Isothiazolone, 5-chloro-2-((4-chlorophenyl)methyl)-, compd. with 2-((4-chlorophenyl)methyl)-3(2H)-isothiazolone (1:1); 5-Chloro-2-(4-chlorobenzyl)-3(2H)-isothiazolone compd. with 2-(4-chlorobenzyl)-3(2H)-isothiazolone (1:1); 3(2H)-Isothiazolone, 5-chloro-2-((4-chlorophenyl)methyl)-, compd. with 2-((4-chlorophenyl)meth; Calcium, dichloro(5-chloro-2-methyl-3(2H)-isothiazolone-O)-, mixt. with dichloro(2-methyl-3(2H)-isothiazolone-O)calcium; Nipacide CI 15; Dichloro(5-chloro-2-methyl-3(2H)-isothiazolone-O)calcium mixt. with dichloro(2-methyl-3(2H)-isothiazolone-O)calcium; isothiazolone; Isothiazole, 1-oxide; 140651-38-3; Isothiazole 1-oxide; ACMC-20mzqf; 1,2-thiazole 1-oxide; 1H-1lambda~4~,2-Thiazol-1-one; NIPACIDE CI 15; 3(2H)-Isothiazolone, 4-hydroxy-5-phenyl-, 1,1-dioxide; ACMC-20lnr0; Mergal K 14; mergal; k; 14; Oprea1_141070; 4-hydroxy-1,1-dioxo-5-phenyl-1,2-thiazol-3-one; 4-hydroxy-5-phenyl-3(2h)-isothiazolone 1,1-dioxide; 4-Hydroxy-5-phenyl-3(2H)-isothiazolone-1,1-dioxide; 3,4-dihydroxy-5-phenyl-1,2-thiazole-1,1-dione; 2-(CHLOROACETYL)-3(2H)-ISOTHIAZOLONE; CMIT/MIT; 3(2H)-Isothiazolone, 2-(chloroacetyl)- (9CI); 5-isopropylsulfonyl-4-phenyl-isothiazol-3-one; 4-phenyl-5-(propane-2-sulfonyl)-isothiazol-3-one; Isothiazalone; thiazol-3-one; 3-isothiazolone; Isothiazol-3-one; 1,2-thiazol-3-one; Isothiazolin-3-one; 3(2H)-Isothiazolone; Isothiazol-3(2H)-one; Isothiazol-3(2H)-one 97%;3-Oxo-2,3-dihydroisothiazole; CMIT/MIT; 4-methyl-1,2-thiazol-3-one; 3(2H)-Isothiazolone,4-methyl-; methyl-3-isothiazolone; 5-Chloro-2-methyl-4-isothiazolin-3-one; 26172-55-4; Methylchloroisothiazolinone; CMIT; 5-Chloro-2-methyl-3(2H)-isothiazolone; CMIT/MIT; 3(2H)-Isothiazolone, 5-chloro-2-methyl-; Kathon CG 5243; 5-chloro-2-methylisothiazol-3(2h)-one; 5-Chloro-2-methyl-2H-isothiazol-3-one; 5-chloro-2-methylisothiazolin-3-one; Mergal K 14; mergal; k; 14; 5-chloro-N-methylisothiazolone

Nipacide CI 15

Nipacide CI is effective against a wide range of microorganisms including gram positive and gram negative bacteria, yeast and fungi. Thermal and pH stability for Nipacide CI is a critical consideration and it should not be used for products with pH >8.5 or production temperatures of >40 °C.

Benefits of Nipacide CI 15
formaldehyde-free
bactericide
fungicide
pH stable 4-9
temperature stable up to 40° C
FDA approved for various applications

Technical data of Nipacide CI 15
Product class   Chloromethyl and methylisothiazolinone, formaldehyde-free
Physical Form   Solution
Active content (ca.)    1.5%
pH stability   4 - 9
Temperature stability    40 °C
Recommended Use Level     0.1 - 0.3%

Regulations and approvals of Nipacide CI 15
FDA 21 CFR 175.105 Adhesives
FDA 21 CFR 176.170 Components of paperboard in contact with aqueous and fatty foods
FDA 21 CFR 176.180 Components of paper and paperboard in contact with dry food.
BfR XIV Plastic dispersions
BfR XXXVI Preservative for Paper and Board

Applications of Nipacide CI 15
Nipacide CI 15 is recommended for preservation of a wide range of applications including:

water based / Latex / PVA adhesives
PVA / Acrylic polymer emulsions
water based decorative paints
printing inks
metal working fluids
construction admixtures

Appearance (20°C) of Nipacide CI 15
Colour
Melting point
Liquid
greenish
approx.0 ℃
Active 1%-2.5%
Boiling point
Density at 20°C
approx.100℃
1.06 g/cm3
pH 2-4
Viscosity dynamic 20mPa.s (20℃)

Profile of Nipacide CI 15
Nipacide CI 15 is water based, low toxicity biocide developed for the complete in-can protection of water based products. Nipacide CI 15 is effective against a wide range of microorganisms including gram positive and gram negative bacteria, yeast and fungi. Microorganisms grow at a rapid rate and without use of the correct biocide, numbers can increase dramatically.

Application of Nipacide CI 15
Nipacide CI 15 is recommended for preservation of a wide range of applications including water based /Latex/PVA adhesives, PVA / Acrylic polymer emulsions, water based decorative paints, printing inks, metal working fluids and construction admixtures. Nipacide CI 15 is effective against a wide range of common spoilage organisms. Thermal and pH stability for Nipacide CI 15 is a critical consideration and it should not be use for
products with pH >9 or production temperatures of >40 C.

Use level of Nipacide CI 15
Nipacide CI 15 should be evaluated in finished products at levels between 0.1% and 0.3%. Please note, however, that the use of Nipacide CI 15 above 0.1% requires R43 (causes sensitization by skin contact) hazard labeling. If labeling is an issue it is recommended you consider an alternative biocide, either CMIT/MIT free or a CMIT/MIT combination biocide eg

Chemical compatibility of Nipacide CI 15
Nipacide CI 15 is compatile with most raw materials used in manufacture of industrial products, Nipacide CI 15 compatibility should aways be checked and evaluated before use.

Nipacide CI 15 is a low toxicity biocide specifically developed for the complete microbiological protection of water based products against bacterial and fungal spoilage in the wet state, particularly where it is to be used at high ambient temperatures. It is a water based clear, yellow liquid. Nipacide CI 15 is recommended for a wide range of applications including adhesives, polymer emulsions, fountain solutions, MWF and paint where protection against fungi and bacteria is required in the wet state.

Nipacide CI 15 is a water based biocide, developed for the complete in-can protection of water based products including water based / Latex/PVA adhesives, PVA / acrylic polymer emulsions, water based decorative paints, printing inks, metal working fluids and construction admixtures.Nipacide CI is effective against a wide range of microorganisms including gram positive and gram negative bacteria, yeast and fungi. Thermal and pH stability for Nipacide CI is a critical consideration and it should not be used for products with pH >8.5 or production temperatures of >40 °C.

USAGE AREAS of Nipacide CI 15
Markets
Building & Construction
Paints & Coatings

Applications of Nipacide CI 15
Building & Construction — Building Materials
Decorative Paints & Coatings
Building & Construction — Building Envelope
Architectural Coatings
Coating Type
Waterborne
Ink Type

Waterborne
Use Level
0.1 - 0.3%
0.1 - 0.3

Properties of Nipacide CI 15
Physical Form
Liquid
Solution

Nipacide CI 15 is a formaldehyde-free blend of chlorinated and non-chlorinated isothiazolinones. Nipacide CI 15 is a low toxicity biocide developed for the complete microbiological protection of water-based products against bacterial and fungal spoilage in the wet state. Designed for decorative paints and printing inks applications. Nipacide CI 15 is approved by FDA regulation.

Area of use
Nipacide CI 15 is often not stable under certain conditions such as high temperatures or high pH values. Normally it is stabilised with Mg, Cu or Na salts. However, some applications are sensitive to salts or electrolyte.
In this case Exocide 1012 AG is an excellent alternative.
This broadband biocide is used to preserve water-based and water-dilutable chemical/technical products, and can be used as an in-can preservative in technical applications such as paints, adhesives, and household and industrial cleaners.
Nipacide CI 15 is especially suitable for preserving fuels such as diesel, or for use in secondary oil production.
This Exocide is also suitable as a slimicide, protective media for liquids in cooling and production systems, and as a protective medium for fluids used in metalworking.
This biocide formulation has a broad antimicrobial spectrum of activity against bacteria, fungi and yeasts and can be used in many cases where other products fail.

Product properties of Nipacide CI 15
Exocide 1012 AG is free of formaldehyde, formaldehyde releasers, phenols and heavy metals, and exhibits excellent chemical stability.
It is not volatile, exhibits outstanding long-term effectiveness, and is one of the best examined broadband biocides.

CMIT and CMI
Nipacide CI 15 (MIT or MI) and Isothiazolinone (CMIT or CMI) are two preservatives from the family of substances called isothiazolinones, used in some cosmetic products and other household products.
MIT can be used alone to help preserve the product or it may be used together with CMIT as a blend.
Preservatives are an essential element in cosmetic products, protecting products, and so the consumer, against contamination by microorganisms during storage and continued use.

MIT and CMIT are two of the very limited number of ‘broad spectrum’ preservatives, which means they are effective against a variety of bacteria, yeasts and moulds, across a wide range of product types.
MIT and CMIT have been positively approved for use as preservatives for many years under the strict European cosmetics legislation.
The primary purpose of these laws is to protect human safety. One of the ways it does this is by banning certain ingredients and controlling others by limiting their concentration or restricting them to particular product types.
Preservatives may only be used if they are specifically listed in the legislation.

Nipacide CI 15 can be used on its own to help preserve cosmetic products.
Following discussions with dermatologists, who reported an increase in cases of allergy to Nipacide CI 15 in their clinics, the European cosmetics industry assessed the available information regarding the risk of allergic reactions to Nipacide CI 15, and in December 2013, the European Personal Care Association, Cosmetics Europe, issued a Recommendation for companies to discontinue the use of MIT in leave-on skincare products.
The European Commission’s independent expert scientific panel (the Scientific Committee on Consumer Safety, SCCS), which advises on safety matters, reviewed the use of MIT in cosmetic products.
In 2013, the SCCS also recommended that MIT be removed from leave-on cosmetic products and that the amount of Nipacide CI 15 used in rinse-off cosmetic products should be reduced.
As a result, the European Commission changed the cosmetic law to ban the use of MIT in leave-on cosmetic products. Since 12 February 2017, it is no longer permitted to make these products available to consumers.
In addition, the maximum amount of MIT present in rinse-off products has been reduced and since 27 April 2018, all products made available to consumers must comply with the new limit.
If consumers have been diagnosed as allergic to Nipacide CI 15 it is important to check the ingredient list of rinse-off cosmetic products. The name ‘Nipacide CI 15’ will always be listed as ‘Nipacide CI 15’ regardless of where in Europe a product is purchased.

Nipacide CI 15 may also be used in a blend with CMIT. If the Nipacide CI 15 and CMIT blend is used to preserve a cosmetic product, then the names Nipacide CI 15 and Nipacide CI 15 will both be present in the ingredients list, which every cosmetic product must have either on its carton, pack or label, card etc. at point of sale.

Applications of Nipacide CI 15
Nipacide CI 15 and other isothiazolinone-derived biocides are used for controlling microbial growth in water-containing solutions.
Two of the most widely used isothiazolinone biocides are 5-chloro-2-methyl-4-isothiazolin-3-one (chloroNipacide CI 15 or CMIT) and 2-methyl-4-isothiazolin-3-one (Nipacide CI 15 or MIT), which are the active ingredients in a 3:1 mixture (CMIT:MIT) sold commercially as Exocide.
Exocide is supplied to manufacturers as a concentrated stock solution containing from 1.5-15% of Nipacide CI 15. For applications the recommended use level is from 6 ppm to 75 ppm active Nipacide CI 15s.
Biocidal applications range from industrial water storage tanks to cooling units, in processes as varied as mining, paper manufacturing, metalworking fluids and energy production.
Nipacide CI 15 also has been used to control slime in the manufacture of paper products that contact food. In addition, this product serves as an antimicrobial agent in latex adhesives and in paper coatings that also contact food.

Developmental/reproductive toxicity
To determine the effects of Nipacide CI 15 on reproductive ability, rats were administered 30, 100, and 300 a.i. ppm of Nipacide CI 15 in drinking water. The control group was administered water and magnesium salt (Table 3). A total of 26 males and females were present in each group. The Nipacide CI 15 concentrations were administered to two generations of rats at 0, 2.8–4.4, 8.5–11.8, and 22.7–28.0 a.i. mg/kg bw/day in the first parental generation (P1), and 0, 4.3–5.5, 13.4–16.0, and 35.7–39.1 a.i. mg/kg bw/day in the second parental generation (P2). In the P1 and P2, concentration-dependent histopathological changes were observed in the stomach. At concentrations of 100 and 300 a.i. ppm, erosion, hyperplasia, and hyperkeratosis were observed. When compared to the control group, neither the female estrus cycle in the P1 and P2 nor the male sperm motility, shape, and number were affected. Moreover, no differences in the other reproductive endpoints compared to the control group were observed. In both generations, gastric irritation was observed at medium and high concentrations; thus, the parental NOAEL of Nipacide CI 15 was set at 30 ppm a.i. (P1: 2.8–4.4 mg/kg bw/day; P2: 4.3–5.5 mg/kg bw/day). The NOEL for reproductive toxicity was set at 300 ppm a.i. (P1: 22.7–28.0 mg/kg bw/day; P2: 35.7–39.1 mg/kg bw/day). No reproductive toxicity up to the highest concentration was noted.
In addition, Nipacide CI 15 was administered via drinking water to 10 male and 10 female rats per group for 15 weeks at concentrations of 0, 25, 75, and 225 ppm. Following this, mating was performed within the same treatment group. No toxicity to parents and fetus was observed at 21 days after delivery.

Furthermore, oral administration experiments were performed in rats at 5 to 15 days of gestation. The experimental groups were treated with Nipacide CI 15 concentrations of 1.5, 4.5, and 15 a.i. mg/kg bw/day, whereas the control group received distilled water. Twenty-five pregnant rats per group were selected in which the dose-dependent maternal toxicity was observed. One rat at low concentrations, two at medium concentrations, and three at high concentrations died due to wheezing, alopecia, and gastric irritation. No other reproductive or teratogenic toxicity was observed. Based on these results, a developmetal NOEL was selected at dose of greater than 15 mg/kg bw/day.
In addition, embryotoxic and fetotoxic effects were reported in rabbits at 6 to 18 days post-pregnancy. Fifteen rabbits per group were administered 0, 1.5, 4.4, and 13.3 a.i. mg/kg bw/day of Nipacide CI 15. This study reported that 0, 5, 12, and 14 rabbits per group, resepectively, were died at these concentrations due to development of ataxia, diarrhea, and severe gastric irritation. A decrease in the number of surviving fetuses, increase in the number of resorption sites, and loss at post-implantation stage were observed. No other treatment-related teratogenic toxicity was observed.
According to the data reported by SCCS (1), additional studies were conducted; however, no detailed information was provided.

Subchronic toxicity
To evaluate the subchronic toxicity, rats were administered following Nipacide CI 15 concentrations: 0, 40–80, 132–260, and 400–800 ppm for 90 days. No systemic toxicity was found to be associated with the treatment, and the NOEL was set at 800 ppm (29.1 a.i. mg/kg bw/day). However, after rats were treated with 0, 25, 75, and 225 a.i. ppm Nipacide CI 15 for 90 days, they showed irritation of the glandular stomach at 225 a.i. ppm. No histopathological changes were observed up to the highest concentration. As a result, the NOEL was set as 75 a.i. ppm, and the no observed adverse effect level (NOAEL) was set as 225 a.i. ppm. Three independent experiments in rats and dogs treated with Nipacide CI 15 for approximately 3 months reported no treatment-related systemic toxicity. After dermal administration of Nipacide CI 15 (0, 0.75, 3.75, and 18.75 mg/kg bw/day) in rats for 91 days, erythema, desquamation, edema, atonia, and eschar formation were observed in all treatment groups. Accordingly, the NOAEL was estimated to be below 0.104 a.i. mg/kg bw/day, and the lowest observed adverse effect level (LOAEL) was estimated to be 0.104 a.i. mg/kg bw/day or higher. No treatment-related systemic toxicity was observed in rabbits’ skin at 0, 100, 200, and 400 a.i. ppm after 13 weeks of treatment . In another experiment, rats exposed to 0, 0.34, 1.15, and 2.64 a.i. mg/m3 Nipacide CI 15 demonstrated irritation of respiratory tract at 1.15 a.i. mg/m3, whereas no histopathological changes were observed up to the highest concentration. Therefore, the NOEL was set at 0.34 a.i. mg/m3, and the NOAEL was restricted to 2.64 a.i. mg/m3.

SUMMARY AND CONCLUSION
In the present study, we performed a risk assessment of Nipacide CI 15, a widely used preservative in cosmetic industry, to confirm its appropriateness for use as per the current safety standards. The results of the non-cancer toxicity assessment in a two-generation reproductive toxicity test revealed an NOAEL of 2.8 mg/kg bw/day, whereas the skin sensitization toxicity test determined the NESIL to be 1.25 μg/cm2/day for humans. When considering of all types of cosmetics, the MOS of non-cancer risk assessment was over 100; however, the AEL/CEL ratio of skin sensitization risk assessment was less than 1, indicating skin sensitization could be a possibility. The AEL/CEL ratio of skin sensitization was calculated to be 2.14225 for rinse-off cosmetics, indicating absence of any dermal risk. In addition, the results of the risk assessment were compared to those of the international risk assessment agency. SCCS selected the NOAEL as 2.8 mg/kg bw/day for the Nipacide CI 15 according to the two-generation reproductive toxicity study in rats. In addition, after evaluating daily rinse-off products containing 0.0015% of Nipacide CI 15, the MOS was calculated to be 7,368, and no safety concern was determined. In addition, the RIVM recommends a quantitative risk assessment of skin sensitizers as a method to ensure safety against skin sensitization. A risk assessment for skin sensitization was performed on 2 to 15 ppm of Nipacide CI 15 in body shampoo/gel, liquid soap, bubble bath, body lotion/cream, shampoo, and eau de toilette. According to the results, the skin sensitization AEL/CEL of the eau de toilette was calculated to be 0.005, which the RIVM considered a safety concern. The CIR did not perform a quantitative risk assessment; however, Nipacide CI 15 was evaluated as safe at concentrations of 15 ppm for rinse-off products and 7.5 ppm for leave-on products based on the cumulative patch test for humans.

At present, Nipacide CI 15 is widely used as a preservative for cosmetics in Korea and Europe. In addition, Nipacide CI 15 serves as a raw material in rinse-off products at a concentration below 0.0015%; however, its use is prohibited in other products (16,17). Based on the results of the risk assessment performed in the present study, the current Nipacide CI 15 regulatory values used in the cosmetics industry are evaluated as appropriate.

Isothiazolinones (also Nipacide CI 15) is a blended biocide with Nipacide CI 15 and Isothiazolinone which carry out the bactericidal effect through breaking the bond of bacteria and algae cell protein. When isothiazolinones contact with microbes, it can quickly break cell protein bond and inhibit their growth, and then lead to the apoptosis of these microbes.

Isothiazolinone products can be effective in controlling both the planktonic and surface growth at very low concentrations and have been produced specifically for oilfield water treatment and paper mill applications.
Nipacide CI 15 has strong biocidal effects on ordinary bacteria, algae and fungi which has many advantages such as no residue, good compatibleness, high stabilization, good degradation, safety and low cost in operation. Isothiazolinone products can mix with other chlorine biocides and most cation, anion, and non-ionic surfactants.

It can be an excellent eco-friendly sludge remover when used at high dosage. Nipacide CI 15 and Isothiazolinone are fungicidal with properties of high efficiency, broad spectrum, non-oxidative and low toxicity. Nipacide CI 15 is the most suitable biocide in industrial circulating cool water systems and in wastewater treatment for oilfield, papermaking, pesticide and other industries. Bichain is one of reliable isothiazolinones manufacturers and suppliers of Nipacide CI 15, CMIT and MIT for oilfield water treatment.
We supply high quality isothiazolinone products with CAS 55965-84-9.