PRODUCTS

CHLORHEXIDINE

CAS NO:55-56-1
EC NO:200-238-7

SYNONYMS:
chlorhexidine; 55-56-1; Rotersept; Fimeil; Hexadol; Soretol; Chlorhexidin; Chlorhexidinum; Chlorohexidine; Nolvasan; Cloresidina [DCIT]; Chlorhexidin [Czech]; Chlorhexidinum [INN-Latin]; Clorhexidina [INN-Spanish]; Hibistat; 1,6-Bis(p-chlorophenyldiguanido)hexane; 1,6-Di(4'-chlorophenyldiguanido)hexane; UNII-R4KO0DY52L; 1,6-Bis(5-(p-chlorophenyl)biguandino)hexane; Exidine; Tubulicid; 1,1'-Hexamethylenebis(5-(p-chlorophenyl)biguanide); 1,1'-Hexamethylene bis(5-(p-chlorophenyl)biguanide); 2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-; Sterilon; CHEMBL790; R4KO0DY52L; MLS001332388; CHEBI:3614; Cloresidina; Clorhexidina; 56-95-1; Biguanide, 1,1'-hexamethylenebis(5-(p-chlorophenyl)-; Chlorhexidine, 98%; CAS-55-56-1; NCGC00016246-03; SMR000857146; Sterido; Savlon babycare; N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)]; DSSTox_CID_13314; DSSTox_RID_79062; N,N'-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide; DSSTox_GSID_33314; Chlorhexidine [INN:BAN]; Chlorhexidine dihydrochloride; MLS001304094; (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexyl]-1-[amino-(4-chloroanilino)methylidene]guanidine; 1-(4-chlorophenyl)-3-[N-[6-[[N-[N-(4-chlorophenyl)carbamimidoyl]carbamimidoyl]amino]hexyl]carbamimidoyl]guanidine; N-(4-chlorophenyl)-1-3-(6-{N-[3-(4-chlorophenyl)carbamimidamidomethanimidoyl]amino}hexyl)carbamimidamidomethanimidamide; CCRIS 9230; Chlorhexidine (INN); C22H30Cl2N10; HSDB 7196; Merfen-incolore (TN); SR-01000799135; Nolvasan (*Diacetate*); 1,1'-Hexamethylenebis(5-[p-chlorophenyl]biguanide); SMR000718621; EINECS 200-238-7; Lisium (*Dihydrochloride*); BRN 2826432; 1,6-Di(N-p-chlorophenyldiguanido)hexane; Dentisept [veterinary] (TN); 1,6-Bis(N5-[p-chlorophenyl]-N1-biguanido)hexane; Prestwick_53; Chlorhexidine (1); Hibidil (Salt/Mix); Hibisol (Salt/Mix); Chlorhexidine diacetate salt hydrate; Hibitane (Salt/Mix); Hibiscrub (Salt/Mix); Hibispray (Salt/Mix); NSC526936; Spectrum_000237; Savloclens (Salt/Mix); Prestwick0_000143; Prestwick1_000143; Prestwick2_000143; Prestwick3_000143; Spectrum2_000135; Spectrum3_000339; Spectrum4_000277; Spectrum5_001322; chlorhexidine diacetate salt; EC 200-238-7; SCHEMBL3984; Chlorhexidine, >=99.5%; BSPBio_000246; BSPBio_001977; KBioGR_000774; KBioSS_000717; 4-12-00-01201 (Beilstein Handbook Reference); MLS001332387444444444444; MLS002154209; DivK1c_000761; SPBio_000210; SPBio_002185; BPBio1_000272; DTXSID2033314; BDBM51937; BDBM64773; cid_9552079; KBio1_000761; KBio2_000717; KBio2_003285; KBio2_005853; KBio3_001197; 2,4,11,13-Tetraazatetradecanediimidamide, N1,N14-bis(4-chlorophenyl)-3,12-diimino-; cid_12303047; NINDS_000761; REGID_for_CID_9552079; BDBM152706; HMS1568M08; HMS2095M08; HMS2233B16; HMS3712M08

Chlorhexidine is a biguanide compound used as an antiseptic agent with topical antibacterial activity. Chlorhexidine is positively charged and reacts with the negatively charged microbial cell surface, thereby destroying the integrity of the cell membrane. Subsequently, chlorhexidine penetrates into the cell and causes leakage of intracellular components leading to cell death. Since gram positive bacteria are more negatively charged, they are more sensitive to this agent.Chlorhexidine is a bisbiguanide compound with a structure consisting of two (p-chlorophenyl)guanide units linked by a hexamethylene bridge. It has a role as an antiinfective agent and an antibacterial agent. It is a member of biguanides and a member of monochlorobenzenes. It derives from a biguanide.Chlorhexidine is a broad-spectrum antimicrobial biguanide used as a topical antiseptic and in dental practice for the treatment of inflammatory dental conditions caused by microorganisms. It is one of the most common skin and mucous membrane antiseptic agents in use today. The molecule itself is a cationic bis-guanide consisting of two 4-chlorophenyl rings and two biguanide groups joined by a central hexamethylene chain. Topical chlorhexidine for disinfection, as well as oral rinses for dental use, carries activity against a broad range of pathogens including bacteria, yeasts, and viruses. Chlorhexidine was developed in the UK by Imperial Chemical Industries in the early 1950s and was introduced to the US in the 1970s.Stable under ambient warehouse conditions to moisture and simulated sunlight.When heated to decomposition, emits very toxic fumes of Cl- and NOX.Solubility in water at 20 °C: >50%.Chlorhexidine is available over-the-counter in various formulations (e.g. solution, sponge, cloth, swab) as a topical antiseptic to sanitize prior to surgeries and/or medical procedures.[L11518,L11521,L11527,L11533] Dental formulations, available by prescription only, include an oral rinse indicated for the treatment of gingivitis[L11512] and a slow-release "chip" which is inserted into periodontal pockets and is indicated for the reduction of pocket depth in adult patients with periodontitis as an adjunct therapy to dental scaling and root planing procedures.To determine if chlorhexidine can be used as an intervention to prolong the time to relapse of oral candidiasis. SUBJECTS AND METHODS: A double-blinded randomized clinical trial was performed in 75 HIV/AIDS subjects with oral candidiasis. Clotrimazole troche was prescribed, and the subjects were re-examined every 2 weeks until the lesions were completely eradicated. The subjects were then randomly divided into two groups; 0.12% chlorhexidine (n = 37, aged 22-52 years, mean 34 years) and 0.9% normal saline (n = 38, aged 22-55 years, mean 38 years). They were re-examined every 2 weeks until the next episode was observed. RESULTS: The time to recurrence of oral candidiasis between the chlorhexidine and the saline group was not statistically significant (P > 0.05). The following variables were significantly associated with the time of recurrence; frequency of antifungal therapy (P = 0.011), total lymphocyte (P = 0.017), alcohol consumption (P = 0.043), and candidiasis on gingiva (P = 0.048). The subjects with lower lymphocyte showed shorter oral candidiasis-free periods (P = 0.034). CONCLUSIONS: Chlorhexidine showed a small but not statistically significant effect in maintenance of oral candidiasis-free period. This lack of significance may be due to the small sample size. Further study should be performed to better assess the size of the effect, or to confirm our findings.Cleanser: As a surgical hand scrub, skin wound and general skin cleanser, health care personnel hand wash, and for preoperative skin preparation. Chlorhedine gluconate significantly reduces the number of microorganisms on the hands and forearms prior to surgery or patient care.For external use only. Keep out of eyes, ears, and mouth. Chlorhexidine gluconate should not be used as a preoperative skin preparation of the face or head. Misuse of products containing chlorhexidine gluconate has been reported to cause serious and permanent eye injury when it has been permitted to enter and remain in the eye during surgical procedures. If chlohexidine gluconate should contact these areas, rinse out promptly and thoroughly with cold water. Avoid contact with neninges. Do not use in genital area.Hypersensitivity reactions: Irritation, sensitization, and generalized allergic reactions have been reported with chlorhexidine-containing products, especially in the genital areas. If adverse reactions occur and last more than 72 hr, discontinue use immediately and, if severe, contact a health care provider.Chlorhexidine gluconate has been reported to cause deafness when instilled in the middle ear through perforate ear drums.Chlorhexidine is a broad-spectrum antimicrobial with demonstrated activity against both gram-positive and gram-negative bacteria, yeasts, and viruses.[A190417] Antimicrobial activity is dose-dependent - chlorhexidine is bacteriostatic at lower concentrations (0.02%-0.06%) and bactericidal at higher concentrations (>0.12%).[A190417] Pharmacokinetic studies of oral chlorhexidine rinses indicate that approximately 30% of the active ingredient is retained in the mouth following rinsing, which is subsequently slowly released into oral fluids.[L11512] This ability to adsorb to dentine, shared with tetracycline antibiotics such as [doxycycline], is known as "substantivity" and is the result of chlorhexidine's positive charge - it is likely that this substantivity plays at least some role in chlorhexidine's antimicrobial activity, as its persistence on surfaces such as dentine prevent microbial colonization.[A190453] Dental chlorhexidine rinses may result in staining of oral surfaces, such as teeth. This effect is not ubiquitous and appears to be more significant with extended therapy (i.e. up to 6 months) - nevertheless, patients for whom oral staining is unacceptable should use chlorhexidine rinse with caution and for the shortest effective interval.[L11512] Allergic reactions to chlorhexidine have been associated with the development of anaphylaxis.Chlorhexidine is a biguanide compound used as an antiseptic agent with topical antibacterial activity. Chlorhexidine is positively charged and reacts with the negatively charged microbial cell surface, thereby destroying the integrity of the cell membrane. Subsequently, chlorhexidine penetrates into the cell and causes leakage of intracellular components leading to cell death. Since gram positive bacteria are more negatively charged, they are more sensitive to this agent.Substances used on humans and other animals that destroy harmful microorganisms or inhibit their activity. They are distinguished from DISINFECTANTS, which are used on inanimate objects.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.Topically, chlorhexidine is unlikely to undergo any degree of systemic absorption. Orally administered chlorhexidine, such as that found in oral rinses for dental purposes, is very poorly absorbed from the gastrointestinal tract - the Cmax in human subjects following an oral dose of 300mg was 0.206 µg/g and occurred approximately 30 minutes after ingestion (Tmax). For tests carried out on whole skin, storage in cutaneous structures after 48 hr was more important than diffusion; the reverse was observed for stripped skin. When the skin was stripped, the amount absorbed was multiplied by approximately 100, and the amount stored in skin by approximately 10. The difference in chlorhexidine diffusion observed between whole and stripped skin was related to the physicochemical characteristics of chlorhexidine.To evaluate the elimination kinetics of chlorhexidine in milk when used as an intramammary infusion to stop lactation in cows. ... The study was performed in 2 phases. Three cows were studied in each phase. All cows were treated with chlorhexidine suspension by infusion into a mastitic mammary gland quarter after 2 milkings 24 hours apart. Foremilk samples (100 mL) were collected from treated and untreated (controls) mammary gland quarters of each cow. Chlorhexidine was extracted from raw milk, and residue concentrations were quantified by use of high-performance liquid chromatography. Foremilk samples from days 2, 5, and 8 were analyzed in phase I, and samples from time 0 and days 3, 7, 14, 21, 28, 35, and 42 were analyzed in phase II. In phases I and II, there was no quantifiable transference of chlorhexidine to milk in untreated mammary gland quarters. Measurable chlorhexidine residues were found in milk from treated mammary gland quarters of 2 cows throughout the 42-day sample period in phase II. Estimated mean elimination half-life for chlorhexidine in milk was 11.5 days.Chlorhexidine’s broad-spectrum antimicrobial effects are due to its ability to disrupt microbial cell membranes. The positively charged chlorhexidine molecule reacts with negatively charged phosphate groups on microbial cell surfaces - this reaction both destroys the integrity of the cell, allowing leakage of intracellular material, and allows chlorhexidine to enter the cell, causing precipitation of cytoplasmic components and ultimately cell death.[L11536,A190453] The specific means of cell death is dependent on the concentration of chlorhexidine - lower concentrations are bacteriostatic and result in leakage of intracellular substances such as potassium and phosphorous, whereas higher concentrations are bactericidal and cause cytoplasmic precipitation.Chlorhexidine is a solid crystal. It will not volatilize and is slightly soluble in water. Salts of chlorhexidine are solid powders. They will not volatilize and are soluble in water. USE: Salts of chlorhexidine are used as disinfectants. Chlorhexidine salts are used in skin and hand disinfectants, skin creams, toothpaste, and deodorants. They are also used as a preservative in eyedrops, wound dressings and antiseptic mouthwashes. Water-based solutions of the salts, chlorhexidine diacetate and chlorhexidine digluconate, are used to control bacteria and viruses on farms, egg handling and packaging equipment, meat and poultry processing plants, and in certain veterinary settings. The chlorhexidine part of these salts is the active antimicrobial ingredient. EXPOSURE: People may be exposed to chlorhexidine by dermal contact or ingestion of antimicrobial products containing salts of this compound. The U.S. EPA requires workers to wear protective clothing and gloves when they are using solutions of chlorhexidine salts to disinfect surfaces. If these solutions are applied as a mist, workers must also wear protective respirators. Dietary exposure to chlorhexidine salts is not expected in the U.S., because workers using the salts to disinfect surfaces in food processing plants are directed to rinse the surfaces with water after treatment. Chlorhexidine is used commercially as its salts which are soluble in water. This reaction can then release chlorhexidine to the environment through direct discharge or discharge to waste water treatment plants. If released to the air, chlorhexidine may be broken down by sunlight. It is not likely to move through soil. Chlorhexidine may not volatilize from soil or water. It is not broken down by microorganisms and is not expected to build up in aquatic organisms. RISK: Direct contact with solutions of chlorhexidine salts can be damaging to eyes and skin. Repeated exposure of the skin of laboratory animals to high doses of solutions of chlorhexidine diacetate salt produced skin damage and liver effects in some animals. Animals given high doses of chlorhexidine diacetate by mouth during pregnancy had decreased body weight gain, but no abortions or birth defects were found. The potential for chlorhexidine salts to produce cancer in laboratory animals has not been tested. The potential for chlorhexidine or its salts to cause cancer in humans has not been assessed by the U.S. EPA IRIS program, the International Agency for Research on Cancer, or the U.S. National Toxicology Program 13th Report on Carcinogens.For chlorhexidine (USEPA/OPP Pesticide Code: 217100) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./For chlorhexidine diacetate (USEPA/OPP Pesticide Code: 045502) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./ /Chlorhexidine diacetate/For chlorhexidine digluconate (USEPA/OPP Pesticide Code: 045504) ACTIVE products with label matches. /SRP: 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./ /Chlorhexidine digluconate/For chlorhexidine dihydrochloride (USEPA/OPP Pesticide Code: 481700) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./ /Chlorhexidine dihydrochloride/Trade names for various chlorhexidine salts and formulations: chlorhexidine: Sterilon, Hibitane, Rotersept; chlorhexidine dihydrochloride: Lisium, Arlacide H, AY-5312; chlorhexidine diacetate: Hibitane diacetate, Novalsan; chlorhexidine digluconate: Abacil, anti Plaque, Arlacide G, Bacticlens, Chlorhexamed, Disteryl, Orahexal, Septeal, Unisept, Corsodyl, Hibiclens, Hibidil, Hibiscrub, Hibitane, Larylin, Peridex, Plac out, Plurexid, Rotersept, Savacol, Solvahex.Nolvasan Solution (Zoetis, Inc.): Active ingredient: chlorhexidine diacetate 2.0%. /Chlorhexidine diacetate/Fort Dodge Nolvasan S (Zoetis, Inc.): Active ingredient: chlorhexidine diacetate 2.0%. /Chlorhexidine diacetate/Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: 2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-. Aggregated National Production Volume: < 500,000 pounds.Chlorhexidine is used primarily as its salts e.g., the dihydrochloride, diacetate, and digluconate in disinfectants (disinfection of the skin and hands), cosmetics (additive to creams, toothpaste, deodorants, and antiperspirants), and pharmaceutical products (preservative in eyedrops, active substance in wound dressings and antiseptic mouthwashes).Three methods are described for the specific determination of chlorhexidine and its salts at various levels in dental creams and related oral materials. The method of measuring the colored reaction product with alkaline sodium hypobromite is less sensitive than that based on hydrolysis of chlorhexidine to give p-chloroaniline. This p-chloroaniline is then reacted with nitrous acid and alpha-naphthol to give a red-colored derivative. The third method is for the determination of submicrogram quantities. After conversion to 1:4 iodochlorobenzene this is determined by electron capture gas chromatography. This method has been applied to the measurement of the uptake of significant amounts of chlorhexidine by dental plaques from a mouthrinse.The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. 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 soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.Waste treatment methods. Product: Offer surplus and non-recyclable solutions to a licensed disposal company. 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. Contaminated packaging: Dispose of as unused product.The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.Precautions for safe handling Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.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. Ensure that the local ventilation moves the contaminant away from the worker.As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Chlorhexidine diacetate is found on List C. Case No: 3038; Pesticide type: antimicrobial; Case Status: RED Approved 06/1995; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): chlorhexidine diacetate; Data Call-in (DCI) Date(s): 03/31/1992; AI Status: OPP has completed a Reregistration Eligibility Decision (RED) for the case/AI. /Chlorhexidine diacetate/As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Chlorhexidine digluconate is found on List C. Case No: 3038; Pesticide type: antimicrobial; Case Status: RED Approved 06/1995; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): chlorhexidine digluconate; AI Status: The active ingredient is no longer contained in any registered products ... "cancelled." /Chlorhexidine digluconate/As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Chlorhexidine dihydrochloride is found on List C. Case No: 3038; Pesticide type: antimicrobial; Case Status: RED Approved 06/1995; OPP has made a decision that some/all uses of the pesticide are eligible for reregistration, as reflected in a Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): chlorhexidine dihydrochloride; AI Status: The active ingredient is no longer contained in any registered products ... "cancelled." /Chlorhexidine dihydrochloride/The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription and over-the-counter drug products, incl chlorhexidine gluconate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.Ophthalmic and topical dosage form new animal drugs. Chlorhexidine. Each gram of ointment contains 10 milligrams chlorhexidine acetate. ... Conditions of use in dogs, cats, and horses - (1) Indications for use. For use as a topical antiseptic ointment for surface wounds. (2) Limitations. Do not use in horses intended for human consumption.Certain other dosage form new animal drugs. Chlorhexidine tablets and suspension. Each tablet and each 28-mL syringe of suspension contain 1 g of chlorhexidine dihydrochloride. ... Indications for use: For prevention or treatment of metritis and vaginitis in cows and mares when caused by pathogens sensitive to chlorhexidine dihydrochloride.Tolerances for residues of new animal drugs in food. A tolerance of zero is established for residues of chlorhexidine in the uncooked edible tissues of calves.Chlorhexidine forms solid crystals. Chlorhexidine diacetate is registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. Currently, two end-use products with 2% chlorhexidine diacetate are registered for use as hard surface-treatment disinfectant/virucides. Chlorhexidine is used primarily as its salts e.g., the dihydrochloride, diacetate, and digluconate in disinfectants (disinfection of the skin and hands), cosmetics (additive to creams, toothpaste, deodorants, and antiperspirants), and pharmaceutical products (preservative in eyedrops, active substance in wound dressings and antiseptic mouthwashes). HUMAN EXPOSURE AND TOXICITY: Chlorhexidine diacetate is highly acutely toxic when applied to the eye. Skin reactions to chlorhexidine-acetate and chlorhexidine-gluconate were tested among eczema patients. Positive reactions were found in 52 (5.4%) of the 1,063 subjects at the initial test. Of these subjects, 29 were retested, and 21 were still found to have positive reactions. Chlorhexidine specific IgE was detected only in Japanese individuals who had experienced anaphylactic type reactions and was not detected in Japanese nurses and patients or in a group of British nurses and hospital staff, all having regular contact with chlorhexidine. All chromogens plus chlorhexidine, but not chlorhexidine alone, produced some discoloration of hydroxyapatite and human teeth. A 67-yr-old man undergoing a colectomy for colon cancer was unintentionally administered 0.8 mg of chlorhexidine gluconate intravenously and subsequently developed acute respiratory distress syndrome. Occupational asthma has been described in two health care workers, as a result of exposure to chlorhexidine and alcohol aerosols. Another case report describes six patients who developed urticaria, dyspnea, and anaphylactic shock due to topical application of chlorhexidine gluconate solution. Even very dilute solutions of chlorhexidine can cause marked chondrolysis of articular cartilage leading to severe permanent damage to the knee. ANIMAL STUDIES: Rabbits suffered severe ocular irritation with chlorhexidine acetate treatment. No dermal irritation was reported up to 72 hours following test article treatment in rabbits. In developmental studies no observable malformations or developmental toxicity were found at any dose level tested. Both positive and negative results have been seen in bacterial studies of the mutagenic effects of chlorhexidine; however, no mutagenic activity was seen in an in-vivo micronucleus assay or a mammalian cytogenic test using Chinese-hamster-ovary cells. No carcinogenic effects were seen in a long term animal study.