ISOTHIAZOLONE COMPOUNDS

Isothiazolone compounds are broad spectrum antimicrobial agents used in cosmetics and personal care products. They are also used as sterilizers in humidifiers and air conditioners, preservatives in carpet cleaners, dishwashing liquids, fabric softeners, floor polishes, general cleaners, sprinkler liquids, slimicides in latex emulsions, cooling tower water, metalworking fluids, oil-field drilling muds, and in paper mills. In the US, current cosmetics and personal care products contain from 0.000004% to 0.01% (100 ppm) of methylisothiazolinone (MIT) as a preservative (Burnett et al, 2010; Bourke et al, 1997). Commercial products for industrial use contain 1.5% to 14.3% before dilution.
BABY WIPES: Some baby wipes contain methylisothiazolinone. Contact dermatitis has been reported in children and their parents who used disposable wipes during diaper changes (Cahill et al, 2014).
FLOOR-CLEANING AGENT: Periorbital erythema and infiltration has been reported in a woman who was exposed to Indur Maxx (R) floor-cleaning agent, containing octylisothiazolinone (Recke et al, 2015).
Kathon CG(R) is a mixture of chloromethylisothiazoline, methylisothiazoline, magnesium salts, and water. It is commonly used as a preservative for water-based cosmetic and toiletry products, both in "wash-off" products such as shampoos, hair conditioners, and liquid soaps, and in "leave-on" products, such as face, hand, and body creams, eye cosmetics, and topical medicaments (S Sweetman , 2002; Cronin et al, 1988).
Isothiazolone compounds have sterilizing properties and are used in humidifier and air conditioning systems (Bourke et al, 1997).
Euxyl 100 (methylchloroisothiazolinone/methylisothiozolinone; MCI/MI; Schylke and Mayr, Hamburg, Germany) is a mixture of 2 isothiazolinones (5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one), magnesium salts and water. Since MCI/MI is effective at very low concentrations against a wide spectrum of bacteria, yeasts, and fungi, it is used both in the industrial and cosmetic industries as a preservative (Mowad, 2000).

FORMS

Kathon CG(R) is a mixture of chloromethylisothiazoline, methylisothiazoline, magnesium salts, and water (S Sweetman , 2002; Cronin et al, 1988).
Approximately 57% of over-the-counter shampoos and conditioners in the United States contain Kathon CG (Fransway, 1988).

-CLINICAL EFFECTS

GENERAL CLINICAL EFFECTS

USES: Isothiazolone compounds are broad spectrum antimicrobial agents used in cosmetics and personal care products. They are also used as sterilizers in humidifiers and air conditioners, preservatives in carpet cleaners, dishwashing liquids, fabric softeners, floor polishes, general cleaners, sprinkler liquids, slimicides in latex emulsions, cooling tower water, metalworking fluids, oil-field drilling muds, and in paper mills. In the US, current cosmetics and personal care products contain from 0.000004% to 0.01% (100 ppm) of methylisothiazolinone (MIT) as a preservative. Commercial products for industrial use contain 1.5% to 14.3% before dilution.

PHARMACOLOGY: Isothiazolones demonstrate antimicrobial activity against gram-positive and gram-negative bacteria, fungi, yeast, and algae.

TOXICOLOGY: Concentrations of 0.06% or less are non-irritant and solutions of 1.5% or more are corrosive. Cosmetics containing as low as 5 to 7 ppm may produce dermatitis in sensitized individuals. Reactions are more likely to occur in patients with pre-existing damaged skin who use "leave-on" cosmetic preparations.

EPIDEMIOLOGY: Exposure is common as these compounds are used in a variety of cosmetics and toiletries; toxicity is very rare. Low concentrations can cause dermatitis in sensitized individuals.

WITH POISONING/EXPOSURE

MILD TO MODERATE TOXICITY: These products can cause gastrointestinal mucosa, respiratory, or eye irritations. Dermal contact also cause irritation and delayed contact dermatitis can develop in sensitized individuals.
SEVERE TOXICITY: In theory, ingestion of undiluted formulations (1.5% or more) could cause caustic injury (marked burns to gastrointestinal mucosa, abdominal pain, gastrointestinal bleeding, and gut perforation). Inhalation or aspiration of undiluted solutions could theoretically cause upper airway edema, stridor, hoarseness, and dyspnea. However, these effects have never been reported. Dermal contact with high concentrations can cause burns.

Editor's Note: An ERG guide with information appropriate to this material does not exist.

-FIRST AID

FIRST AID AND PREHOSPITAL TREATMENT

ORAL EXPOSURE: Prehospital gastrointestinal decontamination is not recommended; toxicity is from irritant/caustic effects, not systemic absorption. Dilution with a small amount of milk or water may be useful if it can be done shortly after ingestion.

DILUTION

If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
USE OF DILUENTS IS CONTROVERSIAL: While experimental models have suggested that immediate dilution may lessen caustic injury (Homan et al, 1993; Homan et al, 1994; Homan et al, 1995), this has not been adequately studied in humans.
DILUENT TYPE: Use any readily available nontoxic, cool liquid. Both milk and water have been shown to be effective in experimental studies of caustic ingestion (Maull et al, 1985; Rumack & Burrington, 1977; Homan et al, 1995; Homan et al, 1994; Homan et al, 1993).
ADVERSE EFFECTS: Potential adverse effects include vomiting and airway compromise (Caravati, 2004).
CONTRAINDICATIONS: Do NOT attempt dilution in patients with respiratory distress, altered mental status, severe abdominal pain, nausea or vomiting, or patients who are unable to swallow or protect their airway. Diluents should not be force fed to any patient who refuses to swallow (Rao & Hoffman, 2002).

DERMAL EXPOSURE: Remove contaminated clothing and wash exposed area thoroughly with soap and water.

EYE EXPOSURE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes.

-RANGE OF TOXICITY

MAXIMUM TOLERATED EXPOSURE

ROUTE OF EXPOSURE

In the US and Europe, the maximum permitted concentration of methylisothiazolinone (MIT) in cosmetics (or as preservative) is 100 ppm (0.01%). Overall, current cosmetics products contain from 0.000004% to 0.01% (100 ppm) of MIT as a preservative (Lundov et al, 2011; Burnett et al, 2010). In one study, many patients allergic to MIT reacted to 50 ppm (Lundov et al, 2011).
MARGIN OF SAFETY: In one study, a margin of safety (MOS) of MIT was determined in a worst case scenario: 100% dermal absorption in a 60-kg individual, the maximum permitted concentration of 100 ppm or 0.1 mg/g, and global daily exposure of 17.79 g/day from all products including multiple cosmetics and personal care products. Using this assumption, a 60-kg individuals will be exposed to 0.0296 mg/kg per day of MIT from all products (0.1 mg/g x 17.79 g/day x 1/60 kg = 0.0296 mg/kg/day) (Burnett et al, 2010).
DERMAL: No acute irritation was seen in humans with 100 ppm (0.67%) dermally, but sensitization has occurred with 25 to 56 ppm, and rarely with 5 to 7 ppm (Hannuksela, 1986). Solutions of 1.5% or greater are corrosive (de Groot & Weyland, 1988).
In 1992, allowable levels of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) was 15 ppm and 7.5 ppm in rinse-off and leave-on products, respectively (Mowad, 2000).

Carcinogenicity Ratings for CAS26172-55-4 :

ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
EPA (U.S. Environmental Protection Agency, 2011): Not Listed
IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
MAK (DFG, 2002): Not Listed
NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

TOXICITY AND RISK ASSESSMENT VALUES

EPA IRIS

EPA Risk Assessment Values for CAS26172-55-4 (U.S. Environmental Protection Agency, 2011):

Not Listed

TOXICITY VALUES

LC50- (INHALATION)RAT:
- 1.4-2 mg/L -- 14% for 4H
- >13.7 mg/L -- 1% for 4H
LD50- (SKIN)RABBIT:
- 660 mg/kg -- 14%
- >5 g/kg -- 1.5%
LD50- (ORAL)RAT:
- 53 mg/kg (RTECS , 2002)
- 60 mg/kg (RTECS , 2002)

-STANDARDS AND LABELS

WORKPLACE STANDARDS

ACGIH TLV Values for CAS26172-55-4 (American Conference of Governmental Industrial Hygienists, 2010):

Not Listed

AIHA WEEL Values for CAS26172-55-4 (AIHA, 2006):

Not Listed

NIOSH REL and IDLH Values for CAS26172-55-4 (National Institute for Occupational Safety and Health, 2007):

Not Listed

OSHA PEL Values for CAS26172-55-4 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

Not Listed

OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS26172-55-4 (U.S. Occupational Safety and Health Administration, 2010):

Not Listed

ENVIRONMENTAL STANDARDS

EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS26172-55-4 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS26172-55-4 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA RCRA Hazardous Waste Number for CAS26172-55-4 (U.S. Environmental Protection Agency, 2010b):

Not Listed
Editor's Note: The D, F, and K series waste numbers and Appendix VIII to Part 261 -- Hazardous Constituents were not included. Please refer to 40 CFR Part 261.

EPA SARA Title III, Extremely Hazardous Substance List for CAS26172-55-4 (U.S. Environmental Protection Agency, 2010):

Not Listed

EPA SARA Title III, Community Right-to-Know for CAS26172-55-4 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):

Not Listed

DOT List of Marine Pollutants for CAS26172-55-4 (49 CFR 172.101 - App. B, 2005):

Not Listed

EPA TSCA Inventory for CAS26172-55-4 (EPA, 2005):

Not Listed

LABELS

NFPA

NFPA Hazard Ratings for CAS26172-55-4 (NFPA, 2002):

Not Listed

-PERSONAL PROTECTION

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

PROTECTIVE CLOTHING

CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 26172-55-4.

Specific recommendations and test data for this chemical were not found in the available manufacturers' product literature. A complete list of consulted manufacturers and references is presented below.

-PHYSICAL HAZARDS

FIRE HAZARD

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

FLAMMABILITY CLASSIFICATION

NFPA Flammability Rating for CAS26172-55-4 (NFPA, 2002):

Not Listed

FIRE CONTROL/EXTINGUISHING AGENTS

Editor's Note: An ERG guide with information appropriate to this material does not exist.

NFPA Extinguishing Methods for CAS26172-55-4 (NFPA, 2002):

Not Listed

EVACUATION PROCEDURES

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

AIHA ERPG Values for CAS26172-55-4 (AIHA, 2006):

Not Listed

DOE TEEL Values for CAS26172-55-4 (U.S. Department of Energy, Office of Emergency Management, 2010):

Not Listed

AEGL Values for CAS26172-55-4 (National Research Council, 2010; National Research Council, 2009; National Research Council, 2008; National Research Council, 2007; NRC, 2001; NRC, 2002; NRC, 2003; NRC, 2004; NRC, 2004; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 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National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 62 FR 58840, 1997; 65 FR 14186, 2000; 65 FR 39264, 2000; 65 FR 77866, 2000; 66 FR 21940, 2001; 67 FR 7164, 2002; 68 FR 42710, 2003; 69 FR 54144, 2004):

Not Listed

NIOSH IDLH Values for CAS26172-55-4 (National Institute for Occupational Safety and Health, 2007):

Not Listed

CONTAINMENT/WASTE TREATMENT OPTIONS

SUMMARY

Editor's Note: An ERG guide with information appropriate to this material does not exist.

SMALL LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

LARGE LEAK/SPILL

Editor's Note: An ERG guide with information appropriate to this material does not exist.

-PHYSICAL/CHEMICAL PROPERTIES

MOLECULAR WEIGHT

METHYLISOTHIAZOLINONE: 115.2 (Burnett et al, 2010)

DESCRIPTION/PHYSICAL STATE

METHYLISOTHIAZOLINONE: Colorless, clear with a mild odor, liquid at 20 degrees C; completely soluble in water; mostly soluble in acetonitrile, methanol, hexane; slightly soluble in xylene (Burnett et al, 2010).

METHYLISOTHIAZOLINONE: 3.87 at 25 degrees C (Burnett et al, 2010)

VAPOR PRESSURE

BOILING POINT

METHYLISOTHIAZOLINONE: 100 degrees C (Burnett et al, 2010)

SOLUBILITY

IN WATER

METHYLISOTHIAZOLINONE: Completely soluble in water (Burnett et al, 2010).

OTHER

METHYLISOTHIAZOLINONE: Mostly soluble in acetonitrile, methanol, hexane; slightly soluble in xylene (Burnett et al, 2010).

-REFERENCES

GENERAL BIBLIOGRAPHY

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40 CFR 372.65: Environmental Protection Agency - Toxic Chemical Release Reporting, Community Right-To-Know, Chemicals and Chemical Categories to which this part applies. National Archives and Records Association (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Apr 3, 2006.

49 CFR 172.101 - App. B: Department of Transportation - Table of Hazardous Materials, Appendix B: List of Marine Pollutants. National Archives and Records Administration (NARA) and the Government Printing Office (GPO), Washington, DC. Final rules current as of Aug 29, 2005.

62 FR 58840: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 1997.

65 FR 14186: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

65 FR 39264: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

65 FR 77866: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2000.

66 FR 21940: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2001.

67 FR 7164: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2002.

68 FR 42710: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2003.

69 FR 54144: Notice of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances - Proposed AEGL Values, Environmental Protection Agency, NAC/AEGL Committee. National Archives and Records Administration (NARA) and the Government Publishing Office (GPO), Washington, DC, 2004.

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ISOTHIAZOLONE COMPOUNDS

Classification | Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents

Information to evaluate chemical incidents