Hexachlorophene

Description

Hexachlorophene (HCP) is a chlorinated bisphenol antiseptic and was introduced for use as an antibacterial component in drug and cosmetic products in 1941. It has bacteriostatic activity against gram-positive organisms (e.g., staphylococcus) but not against gram-negative organisms. HCP is readily absorbed orally and through the skin of humans, especially skin of premature infants or damaged skin. Hexachlorophene is a neurotoxicant, and symptomology may include lethargy, muscle weakness, irritability, cerebral edema, and paralysis leading to coma and death. The US Food and Drug Administration restricted the use of hexachlorophene preparation to ≤0.1% in 1972 and approved it for surgical scrubbing and handwashing. HCP is no longer used extensively in hospitals, rest homes, etc., because of its toxicity.

Chemical Properties

Off-White Crystalline Solid

Chemical Properties

Hexachlorophene is a crystalline solid com pound.

Originator

Gamophen,Ethicon,US,1950

Uses

Used as an antiseptic

Uses

Hexachlorophene is a topical antiseptic in germicidal soaps, creams, deodorants, cleansers, shampoos, after-shave creams, pHisoHex surgical cleanser and in veterinary medicine.

Uses

antiinfective (topical)

Indications

Hexachlorophene is a bacteriostatic antiseptic effective against gram-positive organisms, specifically Staphylococcus. It has a cumulative and sustained effect. Although it has a slow onset of action, with repeated use a film develops on the skin that has long-acting properties. It is not effective against gram-negative organisms or yeast. It is postulated to affect bacterial electron transport and membrane function. With repeated use, it penetrates through the stratum corneum.
It is often used for preoperative surgical scrubbing. One retrospective study showed that it may be teratogenic if used excessively by pregnant women, although there have been no subsequent, well-controlled studies that substantiate this. It should not be used in infants, particularly those who are premature or have dermatoses. It is toxic to tissues when applied to open wounds.

Definition

ChEBI: An organochlorine compound that is diphenylmethane in which each of the phenyl groups is substituted by chlorines at positions 2, 3, and 5, and by a hydroxy group at position 6. An antiseptic that is effective against Gram-positive organisms, it is used in soaps and creams for the treatment of various skin disorders. It is also used in agriculture as an acaricide and fungicide, but is not approved for such use within the European Union.

Preparation

Hexachlorophene is formed by reaction of 2,4,5-trichlorophenol with paraformaldehyde in fuming sulfuric acid (20% SO3) at 65–135 ℃. Hexachlorophene is a strong bacteriostat which also has a microbicidal effect at high concentrations. The use of Hexachlorophene as an antimicrobial agent in cosmetics, medicinal soaps, detergent solutions, and textiles has, however, been discontinued because of its toxicity.

Manufacturing Process

A mixture of 198 grams of 2,4,5-trichlorophenol and 18.8 grams of paraformaldehyde was heated to 65°C and well stirred. 65 grams of oleum 20% was added dropwise and the addition was so regulated that the temperature increased, without the application of external heat, until it reached 135°C at the end of the acid addition, which took 10 to 15 minutes. The contents of the reaction vessel were stirred for 2 minutes more and then allowed to run into a solution of 100 grams of sodium hydroxide in 1,000 cc of water.
The reaction flask was washed with a solution of 25 grams of sodium hydroxide in 250 cc of water. The combined alkaline solutions were heated to boiling for 5 minutes. A small amount (6 grams) of alkali-insoluble material remained and was filtered off. Sulfuric acid (62% H2SO4 content) was then added at room temperature dropwise under stirring to the filtrate until a pH of 10.3 was reached. This required about 80 grams of the acid. The monosodium salt of bis-(3,5,6-trichloro-2-hydroxyphenyl) methane precipitated out of solution and was filtered and then washed with 200 cc of water. The salt was then suspended in 2,000 cc of water and sulfuric acid (62% H2SO4 content) was added under stirring until the contents were acid to Congo red paper. This required about 30 grams of the acid.
The resulting bis-(3,5,6-trichloro-2-hydroxyphenyl) methane was filtered, washed with water until acid-free and dried to constant weight at 100°C (170 grams, MP 154° to 158°C). Crystallization of the 170 grams of dried bis- (3,5,6-trichloro-2-hydroxyphenyl)methane from 300 grams toluene yielded a first crop amounting to 105 grams of substantially pure bis-(3,5,6-trichloro-2- hydroxyphenyl) methane, having a MP of 161° to 163°C (from US Patent 2,435,593).

brand name

Dial (Dial); E-Z Scrub (Becton Dickinson Microbiology); Gamophen (Arabrook); Germa-Medica (Huntington); Hexa-Germ (Huntington); Hexascrub (Prof Dspls); Phiso-Scrub (Sanofi Aventis); Phisohex (Sanofi Aventis); Pre-Op (Davis & Geck); Septi-Soft (Calgon); Septisol (Vestal); Soy-Dome (Bayer); Turgex (Xttrium);99 armour formula;Acnestrol (broparestrol);Acnestrol 3;Akne pyodron kur;Aknefug;Aknelan;Anacal;Asecool;Aserbine cream;Bilvon vet;Bismodyne;Cinthol;Clenisep;Coopaphene;Cordocel-h;Cresophene;Delta pimafucort;Derivative;Derl;Derma 10;Derma leaf;Dermohex;Dermolle;Dexolan;Dial toilet soap;Distocid;Dk 2;Dovaso;Ecto pellicur;Ectofum;Emlab;Fisohen;Fisohexx;Fitty derm;Flenaphthol;Gamophen surgical soap;Germibon;Gill soap;Haemovin;Heksaden;Hepadist;Hexadespon;Hexal;Hexaphenyl(1&b);Hexocreme;Hex-o-san;Jabon antiseptico;Kalacid;Lf 530;Loftyzon;Mamex;Mantacido;Med liquide san t;Micogamma;Nestosyl;P 47;Paradentol;Permucal;Phaisohex;Phasca;Phiso scrub;Phisohex(winthrop);Phiso-med;Phisoscrub;Phlebodine;Phorac;Phosohex;Predekzem;Pretulon;Proct anex;Prodermopur;Sapo-chlor;Sapoderm;Sebbafon;Sebo-cds;Sergi-cen;Skrub kreme;Solu-heks;Steridermis washing cream;Ster-zac antibacterial shaving foam;Ster-zac antibacterial soap;Ster-zac dc skin cleanser;Ster-zac powder;Sumasept;Super sat;Surg salve;Surge vet;Toracsol;Torbetol lotion;Vanseb;Vetalderm;Vulnusol spray;Wesco hex;Wescohex;Westasept;Zalpon antibacterial washing cream.

Therapeutic Function

Topical antiinfective

World Health Organization (WHO)

Hexachlorophene, an antimicrobial agent, was introduced in 1948 in proprietary liquid preparations and powders and was subsequently used extensively as a topical antiseptic. By the early 1970s its use in infants had been conclusively demonstrated to cause encephalopathy as a result of transdermal absorption. More recently it has been suggested that the drug has a teratogenic potential. Many regulatory authorities have placed rigorous restrictions on the medicinal use of hexachlorophene, particularly in preparations intended for infants. However, its use still commonly remains permissible at low concentrations as a preservative in toiletries and cosmetics. (Reference: (WHODI) WHO Drug Information, 3, 6, 1978)

General Description

A white free-flowing odorless powder. Insoluble in water and denser than water. Contact may irritate skin, eyes and mucous membranes. May be toxic by ingestion. Used to make other chemicals.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Hexachlorophene is incompatible with strong oxidizers. Hexachlorophene forms salts with alkalis and alkaline earths.

Hazard

FDA prohibits use unless prescribed by a physician. Questionable carcinogen.

Health Hazard

Inhalation of dust is poisonous; irritating to mucous membranes. Eye and skin irritant. Poisonous if swallowed. Symptoms following ingestion include anorexia, nausea, vomiting, abdominal cramps, and diarrhea. Dehydration may be severe and may be associated with shock.

Potential Exposure

HCP has been used as an antibacterial agent in a wide variety of consumer products, including soaps and deodorants; as a disinfectant. It has also been used as an antifungal agent to treat various citrus fruits and vegetables.

First aid

If this chemical gets into the eyes, remove any con-tact lenses at once and irrigate immediately for at least15 min, occasionally lifting upper and lower lids. Seek medi-cal attention immediately. If this chemical contacts the skin,remove contaminated clothing and wash immediately withsoap and water. Seek medical attention immediately. If this .chemical has been inhaled, remove from exposure, begin res-cue breathing (using universal precautions, including resusci-tation mask) if breathing has stopped and CPR if heart actionhas stopped. Transfer promptly to a medical facility. Whenthis chemical has been swallowed, get medical attention.Give large quantities of water and induce vomiting. Do notmake an unconscious person vomit.

Environmental Fate

HCP adsorbs very strongly to soil and is not expected to leach to groundwater. It may undergo slow photodegradation on the surface of soils and water based on its absorption of light (290 nm). No information is available on its biodegradation in soil or surface water. HCP released in water adsorbs very strongly to sediments and may bioconcentrate in aquatic organisms. It has an estimated bioconcentration factor of 317 000. HCP is not expected to hydrolyze or to significantly evaporate from water. When released into the air, HCP is expected to be mainly in the particle-sorbed state due to its low vapor pressure and high estimated Koc. It is expected to be removed from the atmosphere primarily by dry deposition, but it is also degraded by reaction with photochemically produced hydroxyl radicals, with an estimated vapor phase half-life of 2.5 days.

storage

Color Code- Blue: Health Hazard/Poison: Storein a secure poison location. Prior to working with thischemical you should be trained on its proper handling andstorage. Store in tightly closed containers in a cool,well-ventilated area away from oxidizers.

Shipping

UN2875 Hexachlorophene, Hazard Class: 6.1; Labels: 6.1-Poisonous materials.

Purification Methods

It forms needles from MeOH, C2H4Cl2, or toluene. The diacetate has m 175-176o (EtOH). A disinfectant is also available in MeOH (5mg/L). [Beilstein 6 III 5407, 6 IV 6659.]

Toxicity evaluation

Following skin absorption, HCP enters the nervous system and results in intramyelinic edema, splitting the intraperiod line of myelin in both the central nervous system (CNS) and the peripheral nervous system. Experimental studies with erythrocyte membranes show that HCP binds tightly to cell membranes, resulting in osmotic swelling of erythrocyte membranes by altering their permeability to sodium and potassium. HCP uncouples oxidative phosphorylation.

Incompatibilities

Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explo sions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides.

Waste Disposal

Incineration, preferably after mixing with another combustible fuel. Care must be exercised to assure complete combustion to prevent the formation of phosgene. An acid scrubber is necessary to remove the halo acids produced. Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste con taining this contaminant (≥100 kg/mo) must conform to EPA regulations governing storage, transportation, treat ment, and waste disposal.