5-Chloro-2-methyl-4-isothiazolin-3-one

149.59900

149.60

247-500-7

DEL7T5QRPN

DTXSID9034286

Crystals from ligroin (60-90 °C)

2934999090

50.24000

1.10020

Clear to yellow liquid

1.25 (14% aq.)

52 °C

200.2ºC at 760 mmHg

74.9ºC

n20/D 1.378

In ethyl acetate, 38.06 g/L at 10 deg C

0.328mmHg at 25°C

Henry's Law constant = 4.9X10-9 atm-cu m/mole at 25 °C (est)

Does not dissociate into ions

For a mixture of 5-chloro-2-methyl-3(2H)-isothiazolone and 2-methyl-3(2H)-isothiazolone at 3:1 ratio: Clear golden yellow liquid at 25 °C. Pungent aromatic odor. Boiling point: 101.1 °C; bulk density: 1.296 g/mL at 25 °C; pH: 1.90 at 23.8 °C|Hydroxyl radical reaction rate constant = 2.20X10-11 cu cm/molec-sec at 25 °C (est)

III

8

UN 1760 8/PG 2

1

R20/21/22; R34; R43; R50

S24-S26-S36/37/39-S60-S61

NX8156850

C

Stable. Incompatible with strong oxidizing agents.

P260, P261, P264, P270, P271, P272, P280, P284, P301+P310, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P320, P321, P322, P330, P333+P313, P361, P363, P403+P233, P405, P501

H301

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

5-Chloro-2-methyl-4-isothiazolin-3-one is an indirect food additive for use only as a component of adhesives. 5-Chloro-2-methyl-4-isothiazolin-3-one (CAS Reg. No. 26172-55-4) and 2-methyl-4-isothiazolin-3-one (CAS Reg. No. 2682-20-4) mixture at a ratio of 3 parts to 1 part, manufactured from methyl-3-mercaptopropionate (CAS Reg. No. 2935-90-2). The mixture may contain magnesium nitrate (CAS Reg. No. 10377-60-3) at a concentration equivalent to the isothiazolone active ingredients (weight/weight). Limit: For use only as an antimicrobial agent in polymer latex emulsions.

USEPA/Office of Prevention, Pesticides and Toxic Substances; Reregistration Eligibility Decision Document - Methylisothiazolinone EPA 738-R-98-012 (October 1998). The RED summarizes the risk assessment conclusions and outlines any risk reduction measures necessary for the pesticide to continue to be registered in the U.S.[Available from, as of July 22, 2015: http://www.epa.gov/pesticides/reregistration/status.htm]

|Danger|H300 (20.24%): Fatal if swallowed [Danger Acute toxicity, oral]|P260, P261, P262, P264, P270, P271, P272, P273, P280, P284, P301+P310, P301+P330+P331, P302+P350, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P311, P312, P320, P321, P322, P330, P333+P313, P361, P363, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 2398 companies from 58 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Warning|H317: May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P272, P280, P302+P352, P321, P333+P313, P363, and P501

Microbiocide for oil recovery drilling muds and packer fluids - 0.34 to 34 ppm active ingredient(1).

IDENTIFICATION AND USE: 5-chloro-2-methyl-4-isothiazolin-3-one (CMI) forms crystals. It is used as antimicrobial preservative in cosmetics, hygiene products, paints, emulsions, cutting oils, paper coatings, and water storage and cooling units. CMI is also used in hydraulic fracturing fluids. It is registered for pesticide use in the USA but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. CMI is often used in a combination products with 2-methyl-4-isothiazolin-3-one (MI). HUMAN EXPOSURE AND TOXICITY: Kathon CG, a cosmetics preservative containing, as active ingredients, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, appears to be a frequent cause of contact dermatitis in Europe. ANIMAL STUDIES: A mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMI/MIT) diluted in corn oil was administered by gavage to male and female rats at 0, 0.26, 0.78, 2.33 and 7.0 mg/kg body weight per day. Reduction of serum triglyceride levels in males and induction of hepatic phase 1 xenobiotic metabolizing enzymes in females accompanied by subtle histological changes in the liver were observed at the highest CMIT/MIT exposure. A mixture of CMI/MIT produced point mutations in the absence of a rat-liver metabolizing system in bacteria (strain TA 100) and mammalian cells in culture. In the presence of rat-liver metabolizing system a 10-fold higher concentration was required to induce point mutations in mammalian cells in culture. No mutagenic activity was observed with the metabolizing system and S. typhimurium. Negative results were obtained in the sex-linked recessive lethal assay in Drosophila, the in vivo cytogenetic assay in mice, the unscheduled DNA synthesis assay in cultured rat hepatocytes, and the in vitro cell transformation assay. In immunotoxicity studies CMI, which binds to protein, induced an auricular lymph node cell proliferation response while MI, which poorly binds to protein, neither stimulated a proliferative response nor induced an increase in lymph node size at concentrations similar to CMI.

Previously we reported that brief exposure of HL60 cells to a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one (CMI) and 2-methyl-4-isothiazolin-3-one (MI) shifts the cells into a state of oxidative stress that induces apoptosis and necrosis. In this study, flow cytometric analysis showed that CMI/MI induces early perturbation of calcium homeostasis, increasing cytosolic and mitochondrial calcium and depleting the intracellular endoplasmic reticulum (ER) stores. The calcium chelator BAPTA-AM reduced necrosis and secondary necrosis, the loss of DeltaPsim and S-glutathionylation induced by necrotic doses of CMI/MI, but did not protect against CMI/MI-induced apoptosis, mitochondrial calcium uptake and mitochondrial hyperpolarization. This indicates that increased cytoplasmic calcium does not have a causal role in the induction of apoptosis, while cross-talk between the ER and mitochondria could be responsible for the induction of apoptosis. GSH-OEt pretreatment, which enhances cellular GSH content, reduced S-glutathionylation and cytosolic and mitochondrial calcium levels, thus protecting against both apoptosis and necrosis shifting to apoptosis. Therefore, the degree of GSH depletion, paralleled by the levels of protein S-glutathionylation, may have a causal role in increasing calcium levels. The mitochondrial calcium increase could be responsible for apoptosis, while necrosis is associated with cytoplasmic calcium overload. These findings suggest that S-glutathionylation of specific proteins acts as a molecular linker between calcium and redox signalling.

5-Chloro-2-methyl-4-isothiazolin-3-one's production and use as a preservative in cosmetics such as shampoos, conditioners, gels and surfactants(1) may result in its release to the environment through various waste streams(SRC). Its use as a biocide in industrial water treatment, wood treatment, oil drilling muds(2), hydraulic fracturing fluids(3) and in household products(1) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), measured Koc values ranging from 30-144(2) indicate that 5-chloro-2-methyl-4-isothiazolin-3-one is expected to have very high to high mobility in soil(SRC). Volatilization of 5-chloro-2-methyl-4-isothiazolin-3-one from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.9X10-9 atm-cu m/mole(SRC), derived from its vapor pressure, 0.018 mm Hg(2), and water solubility, 7.3X10+5 mg/L(3). 5-Chloro-2-methyl-4-isothiazolin-3-one is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(2). Utilizing a CO2 evolution test with an activated sludge inoculum, 5-chloro-2-methyl-4-isothiazolin-3-one reached 38.8% and 62.0% CO2 evolution, at initial concentrations of 0.3 and 0.03 ppm, respectively, over a 28 day incubation period(4); the results classified the compound as inherently biodegradable and demonstrated a dependence on concentration(4). 5-Chloro-2-methyl-4-isothiazolin-3-one had a half-life of 5.4 days in a sandy loam soil(2). Results of microcosm studies have shown that biodegradation is the main degradation mechanism(4). Hydrolysis is not important at acidic or neutral pHs, but may have some importance in alkaline soils(4).|AQUATIC FATE: Based on a classification scheme(1), measured Koc values ranging from 30-144 in soil and 310 in sediments(2) indicate that 5-chloro-2-methyl-4-isothiazolin-3-one is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.9X10-9 atm-cu m/mole(SRC), derived from its vapor pressure, 0.018 mm Hg(2), and water solubility, 7.3X10+5 mg/L(4). According to a classification scheme(5), a measured BCF of 5 in bluegill sunfish(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). At 25 °C, 5-chloro-2-methyl-4-isothiazolin-3-one did not hydrolyze at pH 5 or 7 over 30 days(2); a hydrolysis half-life of 22 days was observed at pH 9 under similar conditions(2). Utilizing microcosm studies with a river water and sediment inoculum, a half-life of 17 days under aerobic conditions was determined(6), suggesting that biodegradation is an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 5-chloro-2-methyl-4-isothiazolin-3-one, which has a vapor pressure of 0.018 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 5-chloro-2-methyl-4-isothiazolin-3-one is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 18 hours(SRC), calculated from its rate constant of 2.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Vapor-phase 5-chloro-2-methyl-4-isothiazolin-3-one is also degraded in the atmosphere by reaction with ozone(SRC); the half-life for this reaction in air is estimated to be 46 days(SRC), calculated from its rate constant of 2.5X10-19 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Aqueous photolysis studies have demonstrated that 5-chloro-2-methyl-4-isothiazolin-3-one is susceptible to direct photolysis in sunlight (half-life of 158 hours at surface water conditions)(4).

The rate constant for the vapor-phase reaction of 5-chloro-2-methyl-4-isothiazolin-3-one with photochemically-produced hydroxyl radicals has been estimated as 2.2X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 18 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of 5-chloro-2-methyl-4-isothiazolin-3-one with atmospheric ozone has been estimated as 2.5X10-19 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1); this corresponds to an atmospheric half-life of about 46 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Based upon a UV maximum of 277 nm in methanol with a log epsilon of 3.82(2), 5-chloro-2-methyl-4-isothiazolin-3-one is expected to absorb at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight(SRC). In aqueous photolysis studies conducted in a pH 7 phosphate buffer using natural sunlight, 5-chloro-2-methyl-4-isothiazolin-3-one had a photolysis half-life of 158 hours(3). In an aqueous hydrolysis study, ring-labeled [4,5-14C][5-chloro-2-methyl-4-isothiazolin-3-one], at 10.9-11.4 ppm, did not hydrolyze in sterile pH 5 and 7 aqueous buffered solutions that were incubated in the dark at 25.0 °C for 30 days(4); 5-chloro-2-methyl-4-isothiazolin-3-one degraded with a half-life of 22 days in pH 9 buffered solutions when incubated under similar conditions(4).

A BCF of 5 was determined in bioaccumulation studies performed with bluegill sunfish(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Ring-labeled [4,5-14C][5-chloro-2-methyl-4-isothiazolin-3-one] was very mobile in sandy loam, silt loam, clay loam, and sand soils under aerobic conditions; with Freundlich Kd values of 0.1-1.5, and in sandy loam sediment with a Freundlich Kd value of 4.9 being measured(1). Koc values were 30-144 for the soils and 310 for the sediment(1). According to a classification scheme(2), these Koc values suggest that 5-chloro-2-methyl-4-isothiazolin-3-one is expected to have very high to high mobility in soil and moderate mobility in sediment.

The Henry's Law constant for 5-chloro-2-methyl-4-isothiazolin-3-one is estimated as 4.9X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 0.018 mm Hg(1), and water solubility, 7.3X10+5 mg/L(2). This Henry's Law constant indicates that 5-chloro-2-methyl-4-isothiazolin-3-one is expected to be essentially nonvolatile from water surfaces(3). 5-Chloro-2-methyl-4-isothiazolin-3-one's estimated Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). 5-Chloro-2-methyl-4-isothiazolin-3-one is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

According to the 2012 TSCA Inventory Update Reporting data, 1 reporting facility estimated the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of 5-chloro-2-methyl-4-isothiazolin-3-one in the United States may be <10; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).|NIOSH (NOES Survey 1981-1983) has statistically estimated that 42,106 workers (17,003 of these were female) were potentially exposed to 5-chloro-2-methyl-4-isothiazolin-3-one in the US(1). Occupational exposure to 5-chloro-2-methyl-4-isothiazolin-3-one may occur through inhalation and dermal contact with this compound at workplaces where 5-chloro-2-methyl-4-isothiazolin-3-one is produced or used. Monitoring and use data indicate that the general population may be exposed to 5-chloro-2-methyl-4-isothiazolin-3-one via inhalation of air near consumer products and dermal contact with consumer products, such as cosmetics, containing 5-chloro-2-methyl-4-isothiazolin-3-one(SRC).

Methylchloroisothiazolinone is approved for use within allergenic epicutaneous patch tests which are indicated for use as an aid in the diagnosis of allergic contact dermatitis (ACD) in persons 6 years of age and older.

Substances used on inanimate objects that destroy harmful microorganisms or inhibit their activity. Disinfectants are classed as complete, destroying SPORES as well as vegetative forms of microorganisms, or incomplete, destroying only vegetative forms of the organisms. They are distinguished from ANTISEPTICS, which are local anti-infective agents used on humans and other animals. (From Hawley's Condensed Chemical Dictionary, 11th ed) (See all compounds classified as Disinfectants.)|Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. (See all compounds classified as Anti-Infective Agents.)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ The preservative Kathon CG is a commercial preparation, consisting of 2 active ingredients and other components. 28 patients with contact allergy to Kathon CG participated in a study in which patch testing was performed with serial dilutions, and with 5 chromatographically separated fractions. All reacted to fraction IV, and 2 patients also to fraction II. Mass spectrometry and nuclear magnetic resonance spectrometry identified fraction II and IV to be the active ingredients; 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one. /Mixture/|/EPIDEMIOLOGY STUDIES/ The frequency of sensitization to methylchloroisothiazolinone (MCI)/ methylisothiazolinone (MI) observed in the Information Network of Departments of Dermatology (IVDK) was constantly around 2.1% from 1998 to 2009. After that, it increased to 3.9% in 2011, paralleled by an increase in the frequency of allergic reactions to MI in the preservative series from 1.9% in 2009 to 4.4% in 2011. MI without MCI has increasingly been used as a preservative in cosmetics and skin care products in recent years. /The objective of the study was/ to epidemiologically investigate the possible reasons for this development and to analyze concomitant reactions to MCI/MI and MI. A retrospective analysis of IVDK data from 2009 to 2011 was performed. Stratified data analysis revealed pronounced increases in reactivity to MCI/MI and MI in females, face dermatitis patients, and patients tested because of suspected cosmetic intolerance. The proportion of MI-positive patients among those reacting to MCI/MI increased from 43% to 59% between 2009 and 2011. More widespread consumer exposure has most likely led to the increase in primary sensitization to MI and subsequently to a rise in MCI/MI reactions resulting from immunological cross-reactions ...|/SURVEILLANCE/ Hand eczema is common in children, but affected children are seldom patch tested. Relatively few studies have assessed patch testing in the pediatric population, and none has specifically evaluated its use in hand eczema in children. The aim of this study was to determine the prevalence of contact allergy in children with hand eczema, and to identify the most frequent allergens and their relevance. We performed a 5-year retrospective study of children (aged 0-15 years) with hand eczema tested with the Spanish baseline series at the Dermatology Departments of 11 Spanish hospitals. During the study period, 11 729 patients were patch tested, of whom 480 were children. Hand eczema was present in 111 (23.1%) of the children and in 3437 (30.5%) of the adults. Of the children with hand eczema, 46.8% had at least one positive reaction in the patch tests. Current relevance was found for 78% of the allergens detected. The most common allergens were nickel sulfate, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix I. Allergic contact dermatitis was the most frequent diagnosis (36%), followed by atopic dermatitis ... /Mixture/|/ALTERNATIVE and IN VITRO TESTS/ A 3:1 combination of 5-chloro-2-methyl-4-isothiazolin-3-one (CMI) and 2-methyl-4-isothiazolin-3-one (MI) is widely used to preserve cosmetic products. We show here that CMI/MI induced apoptosis in normal human keratinocytes (NHK) as at low concentrations (0.001-0.05% documented by subdiploid DNA content and phosphatidylserine exposure, while at the highest concentration (0.1% as supplied, 15 p.p.m.) the response was necrosis. Various molecular events accompanied the cytotoxic effects of CMI/MI. Generation of ROS and hyperpolarization of mitochondrial transmembrane potential (DeltaPsim) were early events, followed by increased Fas expression and activation of caspase-8, and then activation of caspase-3 and -9. The drop in DeltaPsim occurred only later in the cell death pathway, when NHK showed signs of apoptosis. Pretreatment of cells for 2 hr with the redox-active agent N-acetyl-L-cysteine conferred complete protection against the CMI/MI-induced cytotoxic effects, DeltaPsim loss, and apoptosis. The pan-caspase inhibitor Z-Val-Ala-Asp(OMe)-CH2F blocked the CMI/MI-induced apoptosis without preventing ROS generation and the drop in DeltaPsim. These results indicate that the generation of ROS plays an important part in mediating apoptosis and necrosis associated with CMI/MI treatment. This new aspect of the in vitro toxicity of CMI/MI may provide important information about the relationship between the preservative's in vitro apoptotic activity and its in vivo toxicity. /Mixture/|For more Human Toxicity Excerpts (Complete) data for 5-Chloro-2-methyl-4-isothiazolin-3-one (6 total), please visit the HSDB record page.

5-chloro-2-methyl-4-isothiazolin-3-one

All of the products containing MIT /Methylisothiazolinone/ and MIT/CMIT /Methylisothiazolinone/Chloromethyliosthiazolinone/ are formulated as ready to use solutions, flowable concentrates and liquid soluble concentrates.|The National Pesticide Information Retrieval System (NPIRS) identifies 32 companies with active labels for products containing the chemical 5-chloro-2-methyl-3(2H)-isothiazolone. To view the complete list of companies, product names and percent 5-chloro-2-methyl-3(2H)-isothiazolone in formulated products click the following url and enter the CAS Registry number in the Active Ingredient field.|Aeroset Water Bath Additive (Abbptt Laboratories): Active ingredient: 5-Chloro-2-methyl-3(2H)-isothiazolone 0.211%; 2-Methyl-3(2H)-isothiazolone 0.075%.|Mergal Mitz (Troy Chemical Company Limited): Active ingredient: 5-Chloro-2-methyl-3(2H)-isothiazolone 1.1%; 2-Methyl-3(2H)-isothiazolone 3.5%.|For more Formulations/Preparations (Complete) data for 5-Chloro-2-methyl-4-isothiazolin-3-one (27 total), please visit the HSDB record page.

3(2H)-Isothiazolone, 5-chloro-2-methyl-: ACTIVE|PMN - indicates a commenced PMN (Pre-Manufacture Notices) substance.|2-Methyl-3(2H)-isothiazolinone and 5-chloro-3-methyl-3(2H)-isothiazolinone occur together in 101 currently registered products in approximately a 3:1 ratio, and are commonly referred to collectively as methylisothiazolinone.

EPA Safer Chemical Functional Use Classes -> Preservatives and Antioxidants|Safer Chemical Classes -> Yellow triangle - The chemical has met Safer Choice Criteria for its functional ingredient-class, but has some hazard profile issues|Cosmetics -> Preservative