5-クロロ-2-メチルイソチアゾール-3(2H)-オン·2-メチルイソチアゾール-3(2H)-オン

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

Preservative

1.35 g/mL at 25 °C

Commercial product is supplied as a clear, light amber liquid, freezing point -18 °C to -21.5 °C; density 1.19 at 20 °C/4 °C; viscosity (23 °C): 5.0 cP. Readily miscible in water, lower alcohols, glycols, other hydrophilic organic solvents. Insoluble in petrolatum /Mixture with methylchloroisothiazolinone/

When heated to decomposition it emits toxic vapors of SOx.

Hazardous decomposition products formed under fire conditions. - Carbon oxides, nitrogen oxides (NOx), Sulphur oxides

FCS -> FDA Cumulative Estimated Daily Intake (CEDI)

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

FCS -> FDA Inventory of Effective Food Contact Substance (FCS) Notifications

FCS -> FDA Inventory of Effective Food Contact Substance (FCS) Notifications

FCS -> FDA Inventory of Effective Food Contact Substance (FCS) Notifications

FCS -> FDA Inventory of Effective Food Contact Substance (FCS) Notifications

Danger

H301: Toxic 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, P320, P321, P330, P333+P317, P361+P364, P362+P364, P363, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 3.7% (92 of 2504) of reports.

Danger

H301+H311 (32.9%): Toxic if swallowed or in contact with skin [Danger Acute toxicity, oral; acute toxicity, dermal]

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

Regulation (EC) No 1935/2004 (amended)

3(2H)-Isothiazolone, 2-methyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 3(2H)-Isothiazolone, 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.

Status: Active Update: 18-11-2021 https://echa.europa.eu/registration-dossier/-/registered-dossier/23868

2-Methyl-3(2H)-isothiazolone: Does not have an individual approval but may be used under an appropriate group standard

Allergic contact dermatitis reported in workers using products containing this preservative; [Kanerva, p. 1815] Danger of skin sensitization; [MAK] Cosmetic preservative that is a recognized contact allergen in consumers; [EC: SCCS - Opinion] Causes burns; Inhalation may cause corrosive injuries to upper respiratory tract and lungs; May cause skin sensitization; Harmful by ingestion; Toxic by inhalation; [Sigma-Aldrich MSDS] See ISOTHIAZOLINONES.

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. 3 (78%)

Acute toxicity (ingestion) - category 3

Acute toxicity (Oral) - Category 3

Acute Tox. 2

Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage.

Air sensitive. Store under inert gas.

Accidental Release Measures. Personal precautions: Wear respiratory protection. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Soak up with inert absorbent material and dispose of as hazardous waste. Keep in suitable, closed containers for disposal.

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.

Product: Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product.

Avoid inhalation of vapor or mist. Normal measures for preventive fire protection.

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.

Hand protection: Handle with gloves.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multi-purpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Eye protection: Tightly fitting safety goggles. Face shield (8-inch minimum). Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin and body protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

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 217 days; oral via capsule 62.7 mg/kg for 14 days (95% confidence interval: 53.2-73.7 mg/kg)

LC50; Species: Anas platyrhynchos (Mallard Duck) age 5 days; chemical incorporated into food 717 ppm for 8 days (95% confidence interval: 442-1133 ppm)

EC50; Species: Daphnia magna (Water Flea) age <24 hr; Conditions: freshwater, flow through; Concentration: 180 ug/L for 48 hr (95% confidence interval: 140-190 ug/L); Effect: intoxication, immobilization /14.17% purity/

For more Ecotoxicity Values (Complete) data for Methylisothiazolinone (7 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 12(SRC), determined from a structure estimation method(2), indicates that methylisothiazolinone is expected to have very high mobility in soil(SRC). Volatilization of methylisothiazolinone from moist soil surfaces is not expected to be an important environmental fate process(SRC) given an estimated Henry's Law constant of 5.0X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Methylisothiazolinone is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.062 mm Hg at 25 °C(3). An aqueous biodegradation half-life of 9 hours(4) suggests that biodegradation may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 12(SRC), determined from a structure estimation method(2), indicates that methylisothiazolinone 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 5.0X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). The hydrolysis half-life for methylisothiazolinone was reported as >30 days at pH 5, 7 and 9(4). According to a classification scheme(5), a reported BCF of 3 in bluegill sunfish(4), suggests bioconcentration in aquatic organisms is low(SRC). Aqueous photodegradation half-life at pH 7 was reported as 11 days for methylisothiazolinone(4). The aqueous aerobic biodegradation half-life of methylisothiazolinone was reported as 9 hours(4), suggesting that biodegradation may be 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), methylisothiazolinone, which has a vapor pressure of 0.062 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase methylisothiazolinone 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 13 hours(SRC), calculated from its rate constant of 2.7X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Methylisothiazolinone is not expected to be susceptible to direct photolysis by sunlight(2).

The Expert Panel for Cosmetic Ingredient Safety concluded that Methylisothiazolinone is safe for use in rinse-off cosmetic products at concentrations up to 100 ppm (i.e. 0.01%) and safe in leave-on cosmetic products when they are formulated to be non-sensitizing, which may be determined based on a QRA or similar methodology.

Safe for use in cosmetics, with qualifications

IDENTIFICATION AND USE: Methylisothiazolinone (MIT) forms colorless prisms. It is used as preservative in personal care and cosmetics products such as leave-on products, namely hand and body lotions and moisturizers, sun tanning lotions and some rinse-off products like shampoos, surfactants and conditioners. In addition, MIT is an antimicrobial used to control slime-forming bacteria, fungi, and algae in cooling water systems, fuel storage tanks, pulp and paper mill water systems, oil extraction systems, and other industrial settings. It is also used to control the growth of mold, mildew, and sapstain on wood products. It is registered for 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. It is often used in a combination products with 5-chloro-2-methyl-4-isothiazolin-3-one. HUMAN EXPOSURE AND TOXICITY: In vitro studies show that a brief exposure to MIT is highly toxic to cultured neurons but not to glia. The toxic actions of this biocide are zinc-dependent and require the activation of p44/42 extracellular signal-regulated kinase (ERK) via a 12-lipoxygenase-mediated pathway. The cell death process also involves activation of NADPH oxidase, generation of reactive oxygen species, DNA damage, and overactivation of poly(ADP-ribose) polymerase, all occurring downstream from ERK phosphorylation. The Cosmetic Ingredient Review Expert Panel noted the in vitro evidence of neurotoxicity but concluded that the absence of any neurotoxicity findings in the many in vivo studies, including subchronic, chronic, and reproductive and developmental animal studies, suggests that MIT would not be neurotoxic as used in cosmetics. Although recognizing that MIT was a sensitizer in both animal and human studies, the panel concluded that there is a threshold dose response and that cosmetic products formulated to contain concentrations of MIT at 100 ppm (0.01%) or less would not be expected to pose a sensitization risk. Accordingly, MIT may be safely used as a preservative in cosmetics up to that concentration. ANIMAL STUDIES: The exposure of rats to MIT at dose levels up to 2.64 mg/cu m via inhalation for 90 days resulted in decreased body weight in the high-dose males and decreased body-weight gains in both sexes at the high-dose level. There were no treatment-related deaths, and no effects were observed in the hematology, clinical chemistry, ophthalmoscopic, and gross pathology parameters that could be attributed to treatment. Similar observations were made when rats were exposed to this chemical (up to 225 ppm) in drinking water for 3 months. In the carcinogenicity study in rats there was no treatment-related increase in the incidence of any tumor in either sex. MIT was not found to be fetotoxic, embryotoxic, or teratogenic in rats. MIT was positive in the Ames assay in TA100 at concentrations as low as 0.0005 uL/plate without metabolic activation. TA100 with activation and all other strains with and without metabolic activation were negative. MIT was positive in the mouse lymphoma gene mutation assay at dose levels as low as 1 nL/mL without metabolic activation and at 1.22 nL/mL with metabolic activation. Negative results were observed in the Drosophila sex-linked recessive lethal assay. MIT did not cause a significant increase in the frequency of structural chromosome aberrations in mouse bone marrow cells in vivo, and did not induce unscheduled DNA synthesis in primary rat hepatocytes in vitro. However, in vitro study in rat cortical neurons found that MIT induced a dramatic inhibition of neurite outgrowth, and concluded that prolonged exposure to low levels of MIT and related compounds may have damaging consequences to the developing nervous system.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of methylisothiazolinone can be estimated to be 12(SRC). According to a classification scheme(2), this estimated Koc value suggests that methylisothiazolinone is expected to have very high mobility in soil.

/HUMAN EXPOSURE STUDIES/ Ninety-eight [98] adult volunteers were enrolled into an intensified Shelanski and Shelanski Repeated Insult Patch Test with KordekTM 50C ( Methyl-4-isothiazolin-3-one; MI), 0.15 mL of a 100 ppm aqueous solution, which was applied to a webril pad to the back of the volunteers under occlusion. Patches were applied four times a week for three weeks [induction phase]. After a week of dosing, the subjects were challenged on a fresh site with MI, 0.15 mL of a 100 ppm aqueous solution applied to a webril pad. One of the 98 subjects showed a positive response [grade 4] on the fifth day of the induction phase. This subject was judged to be pre-sensitised. Of the remaining 97 subjects, none reacted to challenge [elicitation] with 100 ppm aqueous MI. Under the conditions of this test, 100 ppm Methyl-4-isothiazolin-3-one did not induce skin sensitisation in human volunteers.

/HUMAN EXPOSURE STUDIES/ The cumulative irritation potential of 2-Methyl-4-isothiazolin-3-one (RH-573; MI) was - investigated in 21 day test with human volunteers. Aqueous dilutions of MI (0.1 mL) were applied to the back under occlusive patches, for a contact period of 23 hours, on 21 consecutive days. On completion of the dosing phase, the subjects were rested without further dosing for 10 - 14 days. Following the rest period, 24 hour patch(es) of the appropriate test material(s) were applied to a naive site. Subject induced with 50, 100 and 250 ppm MI were challenged with the same respective concentrations of test material as well as distilled water and sodium lauryl sulphate. Subjects induced with 500 ppm MI were challenged with 100, 250 and 500 ppm MI as well as with distilled water and SLS. Four of the subjects induced with 1000 ppm were not only challenged with 1000 ppm but also with 250 and 500 ppm. During the introduction phase, a number of irritant reactions (to both MI and vehicle control - distilled water) were observed, these were mainly graded as 1 and were transient in nature. The total reactions for vehicle controls were 7/16, 4/15, 4/17, 4/15 and 12/16 for the groups I, II, III, IV and V, respectively. No reactions were noted on challenge for the vehicle controls in any group. Cumulative irritation was only observed in one individual from the 1000 ppm induction group. One subject, from the 500 ppm induction group was found to react on challenge. This individual was found to react to the marker pen and also to a number of consumer products; this reaction was therefore considered to equivocal. Two subjects from the 1000 ppm induction group showed a mild reaction upon challenge and were considered to be sensitised. Based on this data the threshold for sensitisation appears to be at or around 1000 ppm 2-Methyl- 4-isothiazolin-3-one.

/HUMAN EXPOSURE STUDIES/ In a Repeat Insult Patch Test, 113 adult volunteers (12 males and 101 females), were enrolled into the study. 0.2 mL of an aqueous solution of 200 ppm 2-Methyl-4-isothiazolin-3-one, was applied by occlusive patches for a contact period of 24-hr per day. Patches were applied three times a week for three weeks [induction phase]. After a week free of dosing, the subjects were challenged on a fresh site with MI, 0.2 mL of a 200 ppm aqueous solution applied to a webril pad. There was no adverse effect reported in the 100 subjects who completed the study. 13 out of 113 enrolled in the study either violated the protocol or withdrew from the study. Under the conditions of this test, 200 ppm Methyl-4-isothiazolin-3-one did not induce skin sensitisation in human volunteers.

/HUMAN EXPOSURE STUDIES/ In a Repeat Insult Patch Test, 107 adult volunteers (19 males and 88 females), were enrolled into the study. 0.2mL of an aqueous solution of 300 ppm 2-Methyl-4-isothiazolin-3-one, was applied by occlusive patches for a contact period of 24-hr per day. Patches were applied three times a week for three weeks [induction phase]. After a week free of dosing, the subjects were challenged on a fresh site with MI, 0.2 mL of a 300 ppm aqueous solution applied to a webril pad. There was no adverse effect reported in the 98 subjects who completed the study. 9 out of 107 enrolled in the study either violated the protocol or withdrew from the study. Under the conditions of this test, 300 ppm Methyl-4-isothiazolin-3-one did not induce skin sensitisation in human volunteers.

For more Human Toxicity Excerpts (Complete) data for Methylisothiazolinone (35 total), please visit the HSDB record page.

Methylisothiazolinone's production and use as a biocide in cooling towers, paper and pulp mills, cosmetics and toiletries, emulsions, plastics, and anti-fouling paints(1) may result in its release to the environment through various waste streams(SRC).

AEROBIC: Utilizing a CO2 evolution test with a freshly prepared activated sludge inoculum, methylisothiazolinone reached 54.1, 55.8 and 47.6% CO2 evolution, at initial concentrations of 0.3, 0.03 and 0.01 ppm, respectively, over a 28 day incubation period; the results classified the compound as inherently biodegradable and demonstrated a dependence on concentration. Microcosm studies in aerobic water found degradation of methylisothiazolinone to be primarily due to biodegradation based on tests using sterile controls. The half-life of methylisothiazolinone in an aerobic microcosm using river water and sediment was 9 days(1).

The Henry's Law constant for methylisothiazolinone is estimated as 5.0X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that methylisothiazolinone is expected to be essentially nonvolatile from moist soil and water surfaces(2). Methylisothiazolinone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.062 mm Hg(3).

/LABORATORY ANIMALS: Acute Exposure/ 2-Methyl-4-isothiazolin-3-one was applied undiluted by a single application of 0.5 mL to the shaved intact skin of 7 New Zealand White rabbits. Contact time was 3 minutes for 5 animals, 1- hr (and 3 min.) for one animal, 4-hr for one animal. The application sites were semi-occluded. After removal of the patch, the animals were observed for 14 days for signs of irritation. No mortality of clinical sign of systemic toxicity were observed during the study. On the 4 and 1 hr sites, skin irritation indicative of corrosivity was observed on day 14 and 7, respectively. On the 3 min. site, very slight to well defined erythema was noted through day 7 and slight edema was noted at 1 hr. The 5 animals exposed during 3 min., very slight to well defined erythema was noted through 48 hr in most rabbits. Very slight to moderate edema was noted at 1 and 24 hr. Very slight to slight edema was noted in one rabbit at 48 and 72 hr. 2-Methyl-4-isothiazolin-3-one is corrosive to the skin when applied undiluted.

/LABORATORY ANIMALS: Acute Exposure/ 0.5 mL of an aqueous solution of NeoloneTM 950 (100 ppm a.i. [MI]) was applied to the skin of a group of six New Zealand White rabbits. Contact time was 4 hours and the application was semioccluded. After removal of the patch, the animals were observed for 72 hours for signs of irritation. No mortality or clinical signs of systemic toxicity were observed during the study. There was no erythema or edema present at any observation period. The Primary Irritation Index (PII) was 0.0.

/LABORATORY ANIMALS: Acute Exposure/ Neolone 950 [9.5% active ingredient in water] was applied to the conjunctival sac of a group of six New Zealand White rabbits, as a 100 ppm aqueous solution (0.1 mL). Eye irritation was evaluated according to Draize criteria at approximately 1, 24, 48, and 72 hours. After the 24 hour observation, each eye (treated and control) was irrigated with 0.9% saline for approximately 60 seconds. No mortality or clinical signs of systemic toxicity were observed. No corneal, conjunctival or iridial effects were observed during the study.

/LABORATORY ANIMALS: Acute Exposure/ The skin sensitisation potential of 2-Methyl-4-isothiazolin-3-one [MI; RH-24,573] was determined using the closed patch method of Buehler [OECD 406]. Four groups of outbred Hartley guinea pigs [5/sex/group] received ten 6-hr induction doses [3 doses/week for 3.5 weeks] of 0.4 mL at concentrations of 1000, 5000, 15,000 and 30,000 ppm a.i. in distilled water. Two weeks after the last induction dose these animals, together with a group of uninduced control animals, were challenged with 1000, 5000, or 15,000 ppm MI in distilled water. No erythema reactions were observed in the non-induced control animals at any challenge concentration of MI. The concentration of MI required to induce and elicit a response in 50 % of the animals (EC50) were estimated to be >/= 5000 ppm a.i. for induction at a challenge concentration 15,000 ppm a.i. and >/= 15,000 ppm a.i. for challenge at an induction concentration of 30,000 ppm a.i.

For more Non-Human Toxicity Excerpts (Complete) data for Methylisothiazolinone (21 total), please visit the HSDB record page.

The rate constant for the vapor-phase reaction of methylisothiazolinone with photochemically-produced hydroxyl radicals has been estimated as 2.7X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 13 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Methylisothiazolinone hydrolysis half-live was reported as >30 days at pH 5, 7 and 9(2). Using natural sunlight and a buffer solution the aqueous photodegradation half-life at pH 7 was reported as 11 days for methylisothiazolinone(2). Methylisothiazolinone is not expected to be susceptible to direct photolysis by sunlight(3).

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.

Neurodegenerative disorders in humans may be triggered or exacerbated by exposure to occupational or environmental agents. ...a brief exposure to methylisothiazolinone, a widely used industrial and household biocide, is highly toxic to cultured neurons but not to glia. /The study/ also show that the toxic actions of this biocide are zinc dependent and require the activation of p44/42 extracellular signal-regulated kinase (ERK) via a 12-lipoxygenase-mediated pathway. The cell death process also involves activation of NADPH oxidase, generation of reactive oxygen species, DNA damage, and overactivation of poly(ADP-ribose) polymerase, all occurring downstream from ERK phosphorylation. The toxic effects of methylisothiazolinone and related biocides on neurons have not been reported previously. Because of their widespread use, the neurotoxic consequences of both acute and chronic human exposure to these toxins need to be evaluated.

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase (PTK) which acts as an early modulator in the integrin signaling cascade. FAK phosphorylation and its consequent activation regulate several basic biological cellular functions. On the contrary, dysregulation of FAK signaling is implicated in the malignant transformation of cells, as well as in nonmalignant pathological conditions. With respect to cytotoxicity, accumulating data indicate that FAK participates in the mechanism of action of the known cytotoxic reactive oxygen species (ROS). Additionally, evidence was presented that different cytotoxic substances, such as arsenic (As), lead (Pb), acrylamide, methylisothiazolinone (MIT), dichlorovinylcysteine (DCVC) and halothane, acted, at least in part, by downregulating FAK tyrosine phosphorylation, while the bacterial toxins Pasteurella multocida toxin and Escherichia coli cytotoxic necrotizing factor, have been shown to exert cytotoxic effects by inducing FAK tyrosine phosphorylation. The observation that upregulation as well as downregulation of FAK activity both result in cytotoxic effects seems contradictory. Even though a common mode of action, with respect to the dysregulation of FAK signaling, for these cytotoxic substances has not yet been discovered, a cumulative approach could be established by focusing on FAK activation and signaling cascade. According to these data, interfering with FAK signaling might be of a potential use in blocking these cytotoxic effects.

Methylisothiazolinone (MIT) is a biocide widely used in industrial and cosmetic products with potential as a neurotoxicant. /it was/ previously reported that short acute exposures to relatively high concentrations of MIT (100 uM) lead to widespread and selective neuronal death in vitro. To evaluate the biological properties of chronic exposures to MIT, freshly dissociated rat cortical neurons were continuously exposed to low concentrations (0.1-3 uM) of the biocide in serum-containing media. Although /this study/ observed minimal effects on cell viability, MIT induced a dramatic inhibition of neurite outgrowth. Immunoblotting and immunoprecipitation experiments revealed that focal adhesion kinase (FAK) phosphorylation was primarily affected by the MIT treatment. The phosphorylation level at tyrosines 576 and 861 of FAK was significantly decreased and likely contributed to the overall reduction of tyrosine phosphorylation of this protein. MIT inhibited Src family kinases (SFKs) in cell-free assays and led to the physical dissociation of FAK from the signaling complexes that it normally forms with c-Src and Fyn in developing neurons. High-density neuronal cultures were then employed to increase cell-to-cell contact. This approach resulted in an overall enhancement of SFKs and FAK phosphorylation and could overcome the deficits induced by MIT. This study suggests that a disruption of FAK-SFK complexes due to SFK inhibition leads to FAK dysfunction, with detrimental effects to immature neurons. Prolonged exposure to low levels of MIT and related compounds may have damaging consequences to the developing nervous system.

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&apos;s Condensed Chemical Dictionary, 11th ed)

CIR ingredient: Methylisothiazolinone

Used as a biocide and preservative in cosmetics, paints, and glues; it is present in Kathon KG, MCI/MI, and Euxyl K100; [Kanerva, p. 1815] Used as an antimicrobial in cosmetics, hygiene products, paints, emulsions, cutting oils, paper coatings, and water storage and cooling units; [Merck Index] Used as a biocide in textile production; [Danish Ministry of the Environment] Used as a preservative in pesticide products; [EPA - Inert Reassessments] Used as a biocide in pulp/paper mills, industrial process and cooling water systems, oil field operations, and air cleaner systems, and as a preservative in adhesives, coatings, fuels, metalworking fluids, resin emulsions, paints, and wood products; [Reference #1]

Metal Machining [Category: Heat or Machine]

For 2-methyl-3(2H)-isothiazolone (USEPA/OPP Pesticide Code: 107104) ACTIVE products with label matches. /SRP: Registered for 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./

Marketed in combination with methylchloroisothiazolinone as a broad spectrum biocide.

Antimicrobial preservative in cosmetics, hygiene products, paints, emulsions, cutting oils, paper coatings, and water storage and cooling units.

2023: <25,000 lb

Production volumes for non-confidential chemicals reported under the Inventory Update Rule.[Table#8186]

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, 2-methyl-. National Production Volume: 2,496 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.

Form: Soluble concentrate/liquid, soluble concentrate/solid.

The formulation intermediate and all currently registered end-use products are a combination of 5-chloro-2-methyl-3(2H)-isothiazolone and 2-methyl-3(2H)-isothiazolone in an equilibrium ratio of approximately 3:1.

The National Pesticide Information Retrieval System (NPIRS) identifies 32 companies with active labels for products containing the chemical 2-methyl-3(2H)-isothiazolone. To view the complete list of companies, product names and percent 2-methyl-3(2H)-isothiazolonechlorpyrifos in formulated products click the following url and enter the CAS Registry number in the Active Ingredient field.

For more Formulations/Preparations (Complete) data for Methylisothiazolinone (51 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

Oil and Gas Drilling, Extraction, and Support activities

3(2H)-Isothiazolone, 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.