Hexachlorophene, also known as Nabac, is an

organochlorine compound An organochloride, organochlorine compound, chlorocarbon, or chlorinated hydrocarbon is an organic compound containing at least one covalent bond, covalently bonded atom of chlorine. The chloroalkane class (alkanes with one or more hydrogens subst ...

that was once widely used as a

disinfectant A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than st ...

. The compound occurs as a white odorless solid, although commercial samples can be off-white and possess a slightly

phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it req ...

ic odor. It is insoluble in water but dissolves in

acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

diethyl ether Diethyl ether, or simply ether, is an organic compound in the ether class with the formula , sometimes abbreviated as (see Pseudoelement symbols). It is a colourless, highly volatile, sweet-smelling ("ethereal odour"), extremely flammable liq ...

, and

chloroform Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...

. In

medicine Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pract ...

, hexachlorophene is useful as a

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

anti-infective, anti-bacterial agent, often used in soaps and toothpaste. It is also used in agriculture as a soil

fungicide Fungicides are biocidal chemical compounds or biological organisms used to kill parasitic fungi or their spores. A fungistatic inhibits their growth. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality, ...

plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...

bactericide A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria. Bactericides are disinfectants, antiseptics, or antibiotics. However, material surfaces can also have bactericidal properties based solely on their ...

, and acaricide.

Removal from market

French deaths

In 1972, the "Bébé" brand of

baby powder Baby powder is an astringent powder used for preventing diaper rash and for cosmetic uses. It may be composed of talc (in which case it is also called talcum powder) or corn starch. It may also contain additional ingredients like fragrances. Ba ...

in France killed 39 babies. It also did great damage to the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

s of several hundred other babies. The batch of toxic "Bébé" brand of powder was mistakenly manufactured with 6% hexachlorophene. This industrial accident directly led to the removal of hexachlorophene from consumer products worldwide.

United States

In 1972, the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) halted production and distribution of products containing more than 1% of hexachlorophene.''

Germicide An antiseptic (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") is an antimicrobial substance or compound that is applied to living tissue/skin to reduce the possibility of infection, sepsis, or putre ...

Limit Stirs Confusion'', New York Times, September 24, 1972, pg. 53. After that change, most products containing hexachlorophene were available only with a doctor's prescription.The Milwaukee Sentinel: "US Order Curbs Hexachlorophene" (UPI), September 23, 1972. From Google News.
/ref> The restrictions were enacted after 15 deaths in the United States, and the 39 deaths in France mentioned above, were reported following brain damage caused by hexachlorophene.Ocala Star Banner, "15 Deaths Cited In Use of Germ Killer, Hexachlorophene" (AP), March 21, 1973. From Google News.
/ref> Several companies manufactured over-the-counter preparations which utilised hexachlorophene in their formulations. One product, ''Baby Magic Bath'' by The Mennen Company, was recalled in 1971, and removed from retail distribution. Two commercial preparations using hexachlorophene, ''

pHisoDerm Phisoderm is a skin detergent which assists persons who are allergic to soap and Phisohex, a detergent and sudsless cleanser which prevents the spread of infections. In the 1950s, both Phisoderm and Phisohex were manufactured by Winthrop Laborato ...

'' and ''pHisoHex'', were widely used as antibacterial skin cleansers in the treatment of

acne Acne, also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, black ...

, (with ''pHisoDerm'' developed for those allergic to the active ingredients in ''pHisoHex''). During the 1960s, both were available over the counter in the US. After the ban, ''pHisoDerm'' was reformulated without hexachlorophene, and continued to be sold over-the-counter, while ''pHisoHex'', (which contained 3% hexachlorophene - 3 times the legal limit imposed in 1972), became available as a prescription body wash. In the

European Community The European Economic Community (EEC) was a regional organization created by the Treaty of Rome of 1957,Today the largely rewritten treaty continues in force as the ''Treaty on the functioning of the European Union'', as renamed by the Lisbo ...

countries during the 1970s and 1980s, ''pHisoHex'' remained available over the counter. A related product, ''pHisoAc'', was used as a skin mask to dry and peel away acne lesions whilst ''pHiso-Scrub'', a hexachlorophene-impregnated sponge for scrubbing, has since been discontinued. Several substitute products (including

triclosan Triclosan (sometimes abbreviated as TCS) is an antibiotic, antibacterial and fungus, antifungal agent present in some consumer products, including toothpaste, soaps, detergents, toys, and surgical cleaning treatments. It is similar in its uses a ...

) were developed, but none had the germ-killing capability of hexachlorophene. ( Sanofi-Aventis was the sole manufacturer of ''pHisoHex'', while

The Mentholatum Company The Mentholatum Company, Inc. is a maker of non-prescription health care products founded in 1889 by Albert Alexander Hyde in the United States. It was bought out by Rohto Pharmaceutical Co., a Japanese health care company, in 1988. The Men ...

owns the ''pHisoDerm'' brand today. Sanofi-Aventis discontinued production of several forms of ''pHisoHex'' in August 2009 and discontinued all production of ''pHisoHex'' in September 2013). The formula for Dial soap was modified to remove hexachlorophene after the FDA ended over-the-counter availability in 1972. Bristol-Myers' discontinued Ipana toothpaste brand at one time contained hexachlorophene.

Germany

In Germany, cosmetics containing hexachlorophene have been banned since 1985.

Austria

In Austria, the sale of drugs containing the substance has been banned since 1990.

Production

Hexacholorophene is produced by alkylation of 2,4,5-

trichlorophenol A trichlorophenol is any organochloride of phenol that contains three covalently bonded chlorine atoms. Trichlorophenols are produced by electrophilic halogenation of phenol with chlorine. Different isomers of trichlorophenol exist according to whic ...

with

formaldehyde Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...

. Related antiseptics are prepared similarly, e.g., bromochlorophene and dichlorophene.

Safety

The LD50 (oral, rat) is 59 mg/kg, indicating that the compound is relatively toxic. It is not

mutagen In genetics, a mutagen is a physical or chemical agent that permanently changes nucleic acid, genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can ca ...

ic nor teratogenic according to Ullmann's Encyclopedia, but "embryotoxic and produces some teratogenic effects" according to the International Agency for Research on Cancer.

2,3,7,8-Tetrachlorodibenzodioxin 2,3,7,8-Tetrachlorodibenzo-''p-''dioxin (TCDD) is a polychlorinated dibenzo''-p-''dioxin (sometimes shortened, though inaccurately, to simply 'dioxin')Tuomisto, Jouko (2019) Dioxins and dioxin-like compounds: toxicity in humans and animals, s ...

(TCDD) is always a contaminant in this compound's production. Several accidents releasing many kilograms of TCDD have been reported. The reaction between 2,4,5-

and formaldehyde is exothermic. If the reaction occurs without adequate cooling, TCDD is produced in significant quantities as a byproduct and contaminant. The

Seveso disaster Seveso (; lmo, label= Lombard, Séves ) is a town and ''comune'' in the Province of Monza and Brianza, in the Region of Lombardy. The economy of the town has traditionally been based on the furniture industry. Its name comes from the river of ...

and the Times Beach, Missouri, contamination incident exemplify the industrial hazards of hexachlorophene production.

Trade names

Trade names for hexachlorophene include: ''Acigena'', ''Almederm'', ''AT7'', ''AT17'', ''Bilevon'', ''Exofene'', ''Fostril'', ''Gamophen'', ''G-11'', ''Germa-Medica'', ''Hexosan'', ''K-34'', ''Septisol'', ''Surofene'', ''M3''.

References

{{Antiseptics and disinfectants Teratogens Chloroarenes Antiseptics Phenols