5-클로로-2-메틸-4-이소티아졸린-3-온

Other Uses -> Biocides/Disinfectants

Other Uses -> Biocides/Disinfectants

Cosmetic ingredients (Methylchloroisothiazolinone) -> CIR (Cosmetic Ingredient Review)

Preservative

Solubility in g/100 mL solvent: water, infinite

In water, 706-751 g/L at 20 °C

Solubility in g/100 mL solvent: ethyl acetate, 4.31; methanol, 4.40, toluene, 4.07; hexane, 0.28

In ethyl acetate, 38.06 g/L at 10 °C

FCS -> FDA Cumulative Estimated Daily Intake (CEDI)

FCS -> FDA Inventory of Food Contact Substances Listed in 21 CFR

This chemical does not meet GHS hazard criteria for 1.3% (31 of 2393) of reports.

Danger

H300 (20.2%): Fatal if swallowed [Danger Acute toxicity, oral]

P260, P261, P262, P264, P264+P265, P270, P271, P272, P273, P280, P284, P301+P316, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P319, P320, P321, P330, P333+P317, P361+P364, P362+P364, P363, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2393 reports by companies from 71 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

Chemical: 3(2H)-Isothiazolone, 5-chloro-2-methyl-

3(2H)-Isothiazolone, 5-chloro-2-methyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 3(2H)-Isothiazolone, 5-chloro-2-methyl- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

PMN - indicates a commenced PMN (Pre-Manufacture Notices) substance.

4-Isothiazolin-3-one, 5-chloro-2-methyl-: HSNO Approval: HSR002759 Approved with controls

A skin sensitizer; [PMID 21938525] Danger of skin sensitization; [MAK] See ISOTHIAZOLINONES.

One of the isothiazolinones is methylchloroisothiazolinone/methylisothiazolinone (Kathon CG). It is a mixture of these two isothiazolinone. . . . Nethercott et al. found that 11 of 27 (41%) metalworkers with eczematous dermatitis in an engine parts manufacturing plant developed allergic contact dermatitis due to Kathon 886 MW in metal-working fluids. [Marks, p. 102-3] Occupational asthma reported in an isothiazolinone manufacturing plant; [Malo]

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]

Residues of 2-methyl-4-isothiazolin-3-one (in combination with 5-chloro-2-methyl-4-isothiazolin-3-one) are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: Preservative. Limit: Not more than 0.0022% (22.5 ppm) in the formulation; 0.00022% (or 2.25 ppm) in the final solution applied to growing crops.

Based on the reviews of the generic data for the active ingredients in the case methylisothiazolinone, the Agency has sufficient information on the health effects of methylisothiazolinone and on its potential for causing adverse effects in fish, wildlife, and the environment. The Agency has determined that methylisothiazolinone products, labeled and used as specified in this Document, will not pose unreasonable risks or adverse effects to humans or the environment. Therefore, the Agency concludes that products containing methylisothiazolinone for all uses are eligible for reregistration.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Methyl-4-isothiazolin-3-one is found on List C. Case No: 3092; Pesticide type: antimicrobial; Case Status: RED Approved 06/96; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): methyl-4-isothiazolin-3-one; Data Call-in (DCI) Date(s): 11/03/92; AI Status: OPP has completed a Reregistration Eligibility Decision (RED) for the case/AI.

Acute Tox. 2 (20.2%)

Skin sensitisation - category 1A

Skin sensitization - Category 1A

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.

Residues of 2-methyl-4-isothiazolin-3-one (in combination with 5-chloro-2-methyl-4-isothiazolin-3-one) are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: Preservative. Limit: Not more than 0.0022% (22.5 ppm) in the formulation; 0.00022% (or 2.25 ppm) in the final solution applied to growing crops.

0.3 [mg/m3]

1.8 [mg/m3]

11 [mg/m3]

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.

LC50; Species: Colinus virginianus (Northern Bobwhite Quail) chemical incorporated into food 1000 ppm for 8 days

LC50; Species: Colinus virginianus (Northern Bobwhite Quail) age 12 days; chemical incorporated into food >100 ppm for 8 days

LC50; Species: Colinus virginianus (Northern Bobwhite Quail) age 11 days; chemical incorporated into food 2200 ppm for 8 days

LD50; Species: Colinus virginianus (Northern Bobwhite Quail) age 33 wk; oral via capsule 74.3 mg/kg (95% confidence interval: 46.6-100 mg/kg)

For more Ecotoxicity Values (Complete) data for 5-Chloro-2-methyl-4-isothiazolin-3-one (31 total), please visit the HSDB record page.

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).

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

The Panel concluded that the ingredient mixture MCI/MI is safe in cosmetics when formulated to be non-sensitizing, based on the results of a QRA or similar methodology; however, at no point should concentrations exceed 7.5 ppm in leaveon products or 15 ppm in rinse-off products.

Safe for use in cosmetics, with qualifications

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.

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.

/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'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).

AEROBIC: Utilizing a CO2 evolution test with a freshly prepared 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(1); the results classified the compound as inherently biodegradable and demonstrated a dependence on concentration(1). Microcosm studies found degradation of 5-chloro-2-methyl-4-isothiazolin-3-one to be primarily due to biodegradation based on tests using sterile controls(1). The half-life of 5-chloro-2-methyl-4-isothiazolin-3-one in an aerobic microcosm using river water and sediment was 17 days(1). At 1 ppm, [14C][5-chloro-2-methyl-4-isothiazolin-3-one], ring-labeled at the 4 and 5 carbons, degraded with a half-life of 5.4 hours in sandy loam soil that was incubated in the dark at 24-26 °C for 64 days, and 75% of field moisture capacity(2). 5-Chloro-2-methyl-4-isothiazolin-3-one, present at 100 mg/L, reached 0% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(3); 5-chloro-2-methyl-4-isothiazolin-3-one is a biocide(1), and the high concentration (100 ppm) may have been toxic to the microorganisms(SRC).

ANAEROBIC: Microcosm studies found degradation of 5-chloro-2-methyl-4-isothiazolin-3-one to be primarily due to biodegradation based on tests using sterile controls. The half-life of 5-chloro-2-methyl-4-isothiazolin-3-one was 5 days in an anaerobic microcosm using river water and sediment(1).

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).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Biocides are added to biodiesels to prevent degradation resulting from microbial growth. A 28-day repeated oral dose study was conducted to assess a potential risk arising from ingestion of isothiazolinone biocides in biodiesels. A mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/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. Rat water and food consumption was monitored. At the end of the dosing period, organs were weighed and histological examinations performed. Hematology, serum clinical chemistry and biomarkers of inflammation were assessed. 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. These changes were more indicative of an adaptive, reversible response than overt toxicity. Based on recommended levels for the control of microbial growth in fuels, CMIT/MIT contained in accidentally ingested biodiesels is not expected to represent a significant health risk. /Mixture/

/GENOTOXICITY/ Kathon biocide, an aqueous solution containing a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one in an approximate ratio of 3:1, was tested for mutagenic activity in Salmonella typhimurium, L5178Y mouse lymphoma cells in culture and Drosophila melanogaster. Tests also were conducted for chromosome aberrations in vivo on mouse bone marrow cells, for DNA damage/repair in primary rat hepatocytes in culture, and for morphological transformation in C3H 10T1/2 cells in culture. Kathon biocide 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. /Mixture/

/GENOTOXICITY/ A variety of shampoos, conditioners, skin-care lotions, and other cosmetic products contain the biocide Kathon CG, which is a mixture of two heterocyclic isothiazolinones: methylisothiazolinone and methylchloroisothiazolinone. This mixture and the related biocide, Kathon 886, have been shown to be potent sensitizers and bacterial mutagens. Five cosmetic products that list the components of Kathon on their labels and two that do not were screened for mutagenicity with Salmonella typhimurium TA100 without S-9. Five of these products and Kathon 886 were further evaluated in TA100 without and with S-9. Kathon 886, a cosmetic product that contained Kathon, and thin layer chromatography-separated components of Kathon 886 were identified by GC/MS analysis. Three of the five products that listed Kathon were direct acting mutagens with TA100. The remaining two products were considerably more toxic than the other products and could not be evaluated for mutagenicity. The addition of S-9 reduced toxicity but did not eliminate mutagenicity. The mutagenic evaluation of Kathon 886 resulted in a dose response similar to that seen with some cosmetic products but at a 1,000-fold lower concentration, and activity was also reduced by the addition of S-9 mix. S-9 reduced activity both with and without cofactors present. Thin layer chromatography separation of the components and subsequent identification by GC/MS indicated that methylisothiazolinone was nonmutagenic while methylchloroisothiazolinone was mutagenic. Additionally, a dichlorinated compound was identified which was also mutagenic. In light of these findings and the reported skin sensitization by Kathon CG in various cosmetics, we recommend that additional testing be done to assure the safety of products containing Kathon CG. /Mixture/

/ALTERNATIVE and IN VITRO TESTS/ Biocides are added to biodiesels to inhibit and remove microbial growth. The effects of 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT), a candidate biodiesel biocide, were studied using freshly isolated rat alveolar macrophages (AM) and NR8383 cell line. CMIT markedly inhibited phagocytic oxidative burst as measured by zymosan-induced chemiluminescence, and cellular cytokine secretion as measured by zymosan-induced TNF-alpha secretion. The 50% inhibition concentration (LC(50)) for CMIT was 0.002-0.004 mM for both cellular functions. AM exposed to CMIT for as little as 2 min showed markedly inhibited functions that persisted for at least 5 hr. Sodium metabisulfite was able to partially neutralize the inhibitory activity of CMIT. Cysteine and glutathione, when present at a molar ratio of 2-1 or higher against CMIT, were effective neutralizers, while serine, histidine, alanine, and albumin were without effect. When the AM testing system was used to compare the toxicity of CMIT against three other candidate biodiesel biocides, methylene dithiocyanate (MDC) was found to be of comparable toxicity to CMIT, 2-methyl-4-isothiazolin-3-one (MIT) was much less toxic, and dimethyl acetylenedicarboxylate (DMAD) was non-toxic. Because AM is among the first cell-type exposed to inhaled biodiesel aerosols, the result suggested that CMIT present in biodiesel may produce respiratory effects ...

For more Non-Human Toxicity Excerpts (Complete) data for 5-Chloro-2-methyl-4-isothiazolin-3-one (9 total), please visit the HSDB record page.

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.

Residues of 2-methyl-4-isothiazolin-3-one (in combination with 5-chloro-2-methyl-4-isothiazolin-3-one) are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: Preservative. Limit: Not more than 0.0022% (22.5 ppm) in the formulation; 0.00022% (or 2.25 ppm) in the final solution applied to growing crops.

Based on the reviews of the generic data for the active ingredients in the case methylisothiazolinone, the Agency has sufficient information on the health effects of methylisothiazolinone and on its potential for causing adverse effects in fish, wildlife, and the environment. The Agency has determined that methylisothiazolinone products, labeled and used as specified in this Document, will not pose unreasonable risks or adverse effects to humans or the environment. Therefore, the Agency concludes that products containing methylisothiazolinone for all uses are eligible for reregistration.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Methyl-4-isothiazolin-3-one is found on List C. Case No: 3092; Pesticide type: antimicrobial; Case Status: RED Approved 06/96; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): methyl-4-isothiazolin-3-one; Data Call-in (DCI) Date(s): 11/03/92; AI Status: OPP has completed a Reregistration Eligibility Decision (RED) for the case/AI.

DEL7T5QRPN

METHYLCHLOROISOTHIAZOLINONE

Established Pharmacologic Class [EPC] - Standardized Chemical Allergen

Physiologic Effects [PE] - Increased Histamine Release

Physiologic Effects [PE] - Cell-mediated Immunity

Chemical Structure [CS] - Allergens

Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.

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)

CIR ingredient: Methylchloroisothiazolinone

Kathon preparations are used as preservatives in cosmetics and in many industrial applications: metalworking fluids, latex paints, adhesives, glues, developing solutions, and slime control agents in paper mills. [Marks, p. 102-4] Used as a preservative in leather processing; [PMID 21938525] Exposed workers include house painters, printers, housekeepers, and machinists.

Metal Machining [Category: Heat or Machine]

Isothiazolinones are used as preservatives, biocides, and disinfectants.

Metal Machining [Category: Heat or Machine]

Ceramics making [Category: Hobbies]

2023: <50,000 lb

Non-confidential 2012 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: 3(2H)-Isothiazolone, 5-chloro-2-methyl-. National Production Volume: 4,965 lb/yr.

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.

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

Furniture and Related Product Manufacturing

3(2H)-Isothiazolone, 5-chloro-2-methyl-: ACTIVE

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.