Phenothiazine

log Kow = 4.15

4.15

YELLOW, RHOMBIC LEAFLETS OR DIAMOND-SHAPED PLATES FROM TOLUENE OR BUTANOL

YELLOW PRISMS FROM ALCOHOL

GRAYISH-GREEN TO GREENISH YELLOW POWDER, GRANULES OR FLAKES

Grayish-green to greenish-yellow solid. [insecticide]

less than 1 mg/mL at 68 °F (NTP, 1992)

FREELY SOL IN BENZENE; SOL IN ETHER & IN HOT ACETIC ACID; SLIGHTLY SOL IN ALCOHOL & IN MINERAL OILS; PRACTICALLY INSOL IN PETROLEUM ETHER, CHLOROFORM

VERY SOL IN ACETONE

Water solubilty = 1.59 mg/l at 25 °C

Solubility in water: none

Insoluble

700 °F at 760 mmHg (NTP, 1992)

371 °C @ 760 MM HG

371 °C

700 °F

700 °F

365.9 to 366.6 °F (NTP, 1992)

185.1 °C

185.1 °C

365 °F

365 °F

0 mmHg (approx) (NIOSH, 2024)

0 mmHg (approx)

0 mmHg (approx)

Phenothiazine is a light green to steel-blue powder. Acquires a greenish-brown tint under exposure to sunlight. (NTP, 1992)

Liquid; Dry Powder; Other Solid; Large Crystals

Grayish-green to greenish-yellow solid; [NIOSH]

YELLOW CRYSTALS. TURNS DARK GREEN ON EXPOSURE TO LIGHT.

Grayish-green to greenish-yellow solid.

Grayish-green to greenish-yellow solid. [insecticide]

READILY OXIDIZED BY SUNLIGHT OR WHEN IN PRESENCE OF FINELY DIVIDED INERT CARRIER, ACQUIRING GREENISH-BROWN TINT

SENSITIVE TO AIR & LIGHT

DARKENS TO DEEP OLIVE-GREEN ON EXPOSURE TO LIGHT

It is stable when dry but easily oxidizes when wet.

This chemical does not meet GHS hazard criteria for 0.7% (24 of 3466) of reports.

Warning

H302 (94.2%): Harmful if swallowed [Warning Acute toxicity, oral]；H317 (97.4%): May cause an allergic skin reaction [Warning Sensitization, Skin]；H373 (93.9%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]；H400 (11.9%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410 (11.9%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]；H412 (83.2%): Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P260, P261, P264, P270, P272, P273, P280, P301+P317, P302+P352, P319, P321, P330, P333+P317, P362+P364, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3466 reports by companies from 53 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 24 of 3466 reports by companies.；There are 52 notifications provided by 3442 of 3466 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Chemical: 10H-Phenothiazine

10H-Phenothiazine is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 10H-Phenothiazine 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)

Status: Active Update: 19-01-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/14459；Status: Active Update: 15-03-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/34074

Phenothiazine: Does not have an individual approval but may be used under an appropriate group standard

Flash point data for this chemical are not available, but it is probably combustible. (NTP, 1992)

Combustible. Gives off irritating or toxic fumes (or gases) in a fire.

Excerpt from NIOSH Pocket Guide for Phenothiazine:；Exposure Routes: Inhalation, skin absorption, ingestion, skin and/or eye contact；Symptoms: Itching, irritation, reddening skin; hepatitis, hemolytic anemia, abdominal cramps, tachycardia; kidney damage; skin photophobia (abnormal visual intolerance to light) sensitization；Target Organs: Skin, cardiovascular system, liver, kidneys (NIOSH, 2024)

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Phenothiazine is included on this list.

While petitions for tolerances for negligible residues are pending and until action is completed on the petitions, an interim tolerance of 2 ppm is established for residues of phenothiazine in or on the following raw agricultural commodity(ies): meat, fat, and meat byproducts of cattle.

PHENOTHIAZINE is slowly decomposed by sunlight. (NTP, 1992). Organosulfides are incompatible with acids, diazo and azo compounds, halocarbons, isocyanates, aldehydes, alkali metals, nitrides, hydrides, and other strong reducing agents. Reactions with these materials generate heat and in many cases hydrogen gas. Many of these compounds may liberate hydrogen sulfide upon decomposition or reaction with an acid.

Fires involving this compound should be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Use powder, water spray, foam, carbon dioxide.

Fresh air, rest.

Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer for medical attention if skin irritation occurs.

Rinse with plenty of water (remove contact lenses if easily possible).

Rinse mouth. Seek medical attention if you feel unwell.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.；SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.；INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.；INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

(General first aid procedures)；Eye: Irrigate immediately - If this chemical contacts the eyes, immediately wash (irrigate) the eyes with large amounts of water, occasionally lifting the lower and upper lids. Get medical attention immediately.；Skin: Soap wash promptly - If this chemical contacts the skin, promptly wash the contaminated skin with soap and water. If this chemical penetrates the clothing, promptly remove the clothing and wash the skin with soap and water. Get medical attention promptly.；Breathing: Respiratory support；Swallow: Medical attention immediately - If this chemical has been swallowed, get medical attention immediately.

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.；STORAGE PRECAUTIONS: You should store this compound under refrigerated conditions and protect it from exposure to light. (NTP, 1992)

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants.

MAIN PRECAUTIONS MUST BE DIRECTED @ PREVENTING ACCIDENTAL INGESTION OF MATERIAL DURING MFR & USE. ... PROCESSES SHOULD BE ENCLOSED & LOCAL EXHAUST VENTILATION SHOULD BE APPLIED WHERE DUST WOULD OTHERWISE ESCAPE... FIRE PRECAUTIONS SHOULD BE PROVIDED...

The worker should immediately wash the skin when it becomes contaminated.

The worker should wash daily at the end of each work shift.

For more Preventive Measures (Complete) data for PHENOTHIAZINE (6 total), please visit the HSDB record page.

PREVIOUS DRENCHING WITH CARBON TETRACHLORIDE MAY ALSO SERVE TO INCR ITS TOXICITY.

ANTIOXIDANTS, EG PHENOTHIAZINE, INHIBITED THE MUTAGENICITY OF BENZO(A)PYRENE & SOME OF ITS DERIVATIVES TOWARDS SALMONELLA TYPHIMURIUM STRAIN TA98; THIS INHIBITION WAS CONCN DEPENDENT.

TERRESTRIAL FATE: Based on a recommended classification scheme(1), an estimated Koc value of 4300(SRC), determined from an experimental log Kow(2) and a recommended regression-derived equation(3), indicates that phenothiazine will have slight mobility in soil(SRC). Volatilization of phenothiazine will not be important from moist soil surfaces(SRC) given an estimated Henry's Law constant of 2.8X10-8 atm-cu m/mole(4,SRC), or from dry soil surfaces(SRC) based on an estimated vapor pressure of 8.9X10-7 mm Hg(5,SRC). The adsorptivity of phenothiazine is expected to be sensitive to pH since phenothiazine is a base with a pKa of 2.52(6). According to a MITI biodegradation study(7), biodegradation of phenothiazine will not be an important fate process in soil(SRC).

AQUATIC FATE: Based on a recommended classification scheme(1), an estimated Koc value of 4300(SRC), determined from an experimental log Kow(2) and a recommended regression-derived equation(3), indicates that phenothiazine would adsorb to suspended solids and sediment(SRC). Phenothiazine would be essentially non-volatile from water surfaces based on an estimated Henry's Law constant of 2.8X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4,SRC). Experimental BCF values of 127-660 and 180-528(6) suggest that phenothiazine will bioconcentrate in aquatic organisms(SRC) according to a recommended classification scheme(5). According to a MITI biodegradation study(6), biodegradation of phenothiazine will not be an important fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), phenothiazine, which has an estimated vapor pressure of 8.9X10-7 mm Hg at 25 °C(2,SRC) will exist as both vapor and particulate in the ambient atmosphere. Vapor-phase phenothiazine 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 about 2 hours(3,SRC). Particulate-phase phenothiazine may be physically removed from the air by dry deposition(SRC).

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.；Dermatotoxin - PACD (photoallergic contact dermatitis).；ACGIH Carcinogen - Not Classifiable.

The most common adverse reactions include:；* Extrapyramidal symptoms, including dystonia, parkinsonism, akathisia, and tardive dyskinesia.；* Weight gain；* Orthostatic hypotension can manifest in 75% of patients with potentially increased risk due to diabetes and pre-existing cardiovascular disorders.；* QTc prolongation；* Pseudoparkinsonism most often occurring in women or older patients.；* Seizures；* Delirium；* Psychosis；Rare adverse events:；* Neuroleptic malignant syndrome；* Retinitis pigmentosa；* Cataracts；* Dermatological allergic reactions；* Poikilothermia；* Agranulocytosis；Common less severe adverse events:；* Urinary hesitancy and retention；* Dry mouth,；* Dry eyes

The substance can be absorbed into the body by ingestion.

inhalation, skin absorption, ingestion, skin and/or eye contact

A review of 48 hospital-admitted phenothiazine toxicities with concentrations of 200 mg to 500 mg per patient has listed common reactions such as hypothermia, tachycardia, tachypnea, and decreased diastolic blood pressure. A tendency towards obtundation can present in cases where other drugs were also involved. Furthermore, a pupil size of less than 3 mm was present in the most severe poisoning cases. Prolonged QTc interval was noted, and patients were treated with diphenylhydantoin. An echocardiogram is a suggested approach for all cases of phenothiazine overdoses.；Treatment methods for phenothiazine overdoses included administering ipecac, gastric lavage, intravenous diphenhydramine, and intravenous hydration to reverse extrapyramidal symptoms and absorption. No fatalities occurred, and 50% of the patients were discharged following 24 hours, while the other 50% stayed for an average duration of 3.4 days. Potentially serious complications were present in 71% of the patients who stayed longer than 24 hours; however, all of those patients recovered.

Severe itching. Redness.

Abdominal cramps.

Itching, irritation, reddening skin; hepatitis, hemolytic anemia, abdominal cramps, tachycardia; kidney damage; skin photophobia (abnormal visual intolerance to light) sensitization

The substance is toxic to aquatic organisms. Bioaccumulation of this chemical may occur in fish. The substance may cause long-term effects in the aquatic environment. This substance does enter the environment under normal use. Great care, however, should be taken to avoid any additional release, for example through inappropriate disposal.

The Koc of phenothiazine is estimated as approximately 4300(SRC), using an experimental log Kow of 4.15(1) and a regression-derived equation(2,SRC). According to a recommended classification scheme(3), this estimated Koc value suggests that phenothiazine has slight mobility in soil(SRC). The adsorptivity of phenothiazine is expected to be sensitive to pH since phenothiazine is a base with a pKa of 2.52(4).

In human beings, photosensitization of the skin has been noted, but keratitis has been reported only among workers handling the compound, and in this instance the nature of the keratitis has not been described, and it is not clear whether it is due to mechanical irritation by crystals of the substance or from hydrogen sulfide liberated in its manufacture

OVERDOSAGE (& ACCIDENTAL EXPOSURES) HAVE CAUSED HEMOLYTIC ANEMIA, TOXIC HEPATITIS, SKIN PHOTOSENSITIZATION, & INTENSE PRURITUS BUT APPARENTLY NOT CENTRAL NERVOUS DEPRESSION.

Average or large oral doses of phenothiazine may cause hepatotoxicity, hemolytic anemia, abdominal cramps, and tachycardia. Gastrointestinal and skin irritation, renal damage, skin photosensitization, and pruritus have also been reported.

PHENOTHIAZINE ITSELF HAS HARMFUL IRRITANT PROPERTIES, & INDUSTRIAL EXPOSURE MAY PRODUCE SKIN LESIONS & PHOTOSENSITIZATION INCL PHOTOSENSITIZED KERATITIS.

For more Human Toxicity Excerpts (Complete) data for PHENOTHIAZINE (8 total), please visit the HSDB record page.

Chemical: 10H-Phenothiazine

10H-Phenothiazine is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 10H-Phenothiazine 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)

Status: Active Update: 19-01-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/14459；Status: Active Update: 15-03-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/34074

Phenothiazine: Does not have an individual approval but may be used under an appropriate group standard

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Phenothiazine is included on this list.

While petitions for tolerances for negligible residues are pending and until action is completed on the petitions, an interim tolerance of 2 ppm is established for residues of phenothiazine in or on the following raw agricultural commodity(ies): meat, fat, and meat byproducts of cattle.

SOME PHENOTHIAZINE IS CONVERTED WITHIN GUT TO SOL DERIV, MAINLY PHENOTHIAZINE SULFATE...

YIELDS 3-HYDROXYPHENOTHIAZINE IN DOGS. /FROM TABLE/

THE ANTHELMINTIC, PHENOTHIAZINE, WAS OXIDIZED TO SULFOXIDE BY ENZYMES OF THE PROGLOTTIDS OF THE CESTODE, MONIEZIA EXPANSA & CYTOSOL OF INTESTINAL EPITHELIAL CELLS OF THE NEMATODE ASCARIS SUUM. ENZYMES IN THESE TISSUES ALSO DECR SULFOXIDES TO THIOETHERS IN ABSENCE OF O.

RAT, MOUSE, & GERBIL EXCRETED THE MAJORITY OF PHENOTHIAZINE IN CONJUGATED FORM. THE RAT, MOUSE, & GERBIL PRODUCED LEUCOPHENOTHIAZONE SULFATE AS MAJOR METABOLITE, RELYING MORE ON C-OXIDATION PATHS THAN THE HAMSTER WHICH EXCRETED LARGE AMT OF PHENOTHIAZINE N-GLUCURONIDE.

BECAUSE OF ITS LOW SOLUBILITY, RATE OF ITS ABSORPTION FROM GI TRACT IS DEPENDENT ON PARTICLE SIZE. MICRONIZED FORM OF DRUG IS ABSORBED RAPIDLY.

...ABOUT 30-50% OF ORAL DOSE PASSES THROUGH ALIMENTARY TRACT UNCHANGED. SOME PHENOTHIAZINE IS CONVERTED WITHIN GUT TO SOL DERIV...WHICH ARE ABSORBED INTO PORTAL VENOUS SYSTEM. ...DERIV ARE SECRETED IN URINE & ARE RESPONSIBLE FOR ITS RED COLOR WHEN EXPOSED TO AIR. THEY ALSO APPEAR IN BILE & IN MILK OF LACTATING ANIMALS. URINARY & FECAL EXCRETION OF PHENOTHIAZINE OR ITS DERIV ACCOUNTS FOR 80% OF ORAL DOSE IN SHEEP; FATE OF REMAINING 20% IS UNKNOWN.

URINARY & FECAL EXCRETION OF PHENOTHIAZINE OR ITS DERIV ACCOUNTS FOR 80% OF ORAL DOSE IN SHEEP; FATE OF REMAINING 20% IS UNKNOWN.

ABSORBED BY SKIN.

... Phenothiazine was readily absorbed from the alimentary tract, with the free drug and reddish oxidation products appearing in the urine.

Used to manufacture veterinary anthelmintics and other pharmaceuticals; [Merck Index, #7252]

MFR OF DYES; PARENT CMPD FOR CHLORPROMAZINE & RELATED ANTIPSYCHOTIC DRUGS; POLYMERIZATION INHIBITOR; ANTIOXIDANT

Used in control of insects that breed in manure

Synthesis of promethazine hydrochloride

Polymerization inhibitor for chloroprene

For more Uses (Complete) data for PHENOTHIAZINE (10 total), please visit the HSDB record page.

DISPERSIBLE POWDERS (36%).

GRADES: TECHNICAL; NF.

Printing Ink Manufacturing；All Other Basic Organic Chemical Manufacturing；Plastics Material and Resin Manufacturing；Paint and Coating Manufacturing；Soap, Cleaning Compound, and Toilet Preparation Manufacturing；Plastics Product Manufacturing

10H-Phenothiazine: ACTIVE

PURIFICATION: VIERLING, US PATENT 2,887,482 (1959); RIGBY, US PATENT 3,000,887 (1961 TO SHELL OIL).

/OXIDATION/...CAN BE PREVENTED BY ADMIXTURE OF 0.3-1.0% METHENAMINE.

...PARENT OF NUMBER OF DYESTUFFS INCL METHYLENE BLUE, THIAZINE DYES & THIAMINE BLUE.

INTRODUCED IN 1925, IT WAS ONE OF EARLIEST ORG INSECTICIDES. ACTION: ORAL INSECTICIDE & ANTHELMINTIC. FED IN SALT OR MINERAL SUPPLEMENT TO CONTROL HORN FLY & FACE FLY LARVAE & TO REMOVE & CONTROL CERTAIN INTERNAL PARASITES.