Метилизотиазолинон

FE1250000

C

Stable under recommended storage conditions.

P261-P273-P280-P305 + P351 + P338-P310

H302-H314-H317-H331-H335-H400

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.

Materials to avoid: Strong oxidizing agents, Amines, Mercaptans, Reducing agents.

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|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P260, P261, P264, P270, P271, P272, P273, 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, P391, P403+P233, P405, and P501|H301+H311 (35.35%): Toxic if swallowed or in contact with skin [Danger Acute toxicity, oral; acute toxicity, dermal]|P260, P261, P264, P270, P271, P272, P273, P280, P284, P301+P310, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P312, 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 2440 companies from 91 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P260, P261, P264, P270, P271, P272, P273, P280, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P311, P312, P321, P330, P333+P313, P363, P391, P403+P233, P405, and P501

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.

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special protective equipment for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

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.

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.

Methylisothiazolinone was detected in commercial lotion samples at 3.8-4.1 mg/g(1).

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.

LD50 Rats(female) oral 183 mg/kg bw /RH-573 Technical/|LD50 Rats(male) oral 235 mg a.i./kg bw /RH-573 Technical/|LD50 Rats (male) oral 2834 mg product/kg bw /Neolone 950 Preservative/|LD50 Rats (female) oral 1091 mg product/kg bw /Neolone 950 Preservative/|For more Non-Human Toxicity Values (Complete) data for Methylisothiazolinone (7 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).

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 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).

A BCF of 3 was reported in bluegill sunfish (Lepomis macrochirus) for methylisothiazolinone(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

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.

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).

According to the 2012 TSCA Inventory Update Reporting data, 1 reporting facility estimates the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of methylisothiazolinone in the United States may be as low as <10 workers; 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 56,188 workers (17,605 of these were female) were potentially exposed to methylisothiazolinone in the US(1). In a Danish National Survey conducted in 1989 occupational exposures to methylisothiazolinone were estimated at 250,000 with the highest exposures coming from personal services, cleaning and hair dressing (52,000), manufacture of fabricated metal products (48,000) and health services and pharmacies (24,000). Occupational exposure to methylisothiazolinone may occur through inhalation and dermal contact with this compound at workplaces where methylisothiazolinone is produced or used. Use data indicate that the general population may be exposed to methylisothiazolinone via inhalation of fumes from paint and cleaning products containing the biocide, and dermal contact with consumer products (cleaning products, cosmetics, toiletries) containing methylisothiazolinone(SRC).

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.)|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.)

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.

Impurity (manufacturing by-products)[Table#8194]

/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/