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Chlorhexidine Gluconate

PubChem CID
9552081
Structure
Chlorhexidine Gluconate_small.png
Chlorhexidine Gluconate_3D_Structure.png
Molecular Formula
Synonyms
  • CHLORHEXIDINE DIGLUCONATE
  • Chlorhexidine gluconate
  • 18472-51-0
  • Hibiclens
  • Bioscrub
Molecular Weight
897.8 g/mol
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Dates
  • Create:
    2006-10-23
  • Modify:
    2025-01-04
Description
Chlorhexidine gluconate is an organochlorine compound and a D-gluconate adduct. It has a role as an antibacterial agent. It is functionally related to a chlorhexidine.
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. The FDA withdrew its approval for the use of chlorhexidine gluconate topical tincture 0.5%, due to a significant number of reports concerning chemical and thermal burns associated with the use of this product. Other formulations of chlorhexidine continue to be available.
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.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Chlorhexidine Gluconate.png

1.2 3D Conformer

3D Conformer of Parent

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexyl]-1-[amino-(4-chloroanilino)methylidene]guanidine;(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2024.11.20)

2.1.2 InChI

InChI=1S/C22H30Cl2N10.2C6H12O7/c23-15-5-9-17(10-6-15)31-21(27)33-19(25)29-13-3-1-2-4-14-30-20(26)34-22(28)32-18-11-7-16(24)8-12-18;2*7-1-2(8)3(9)4(10)5(11)6(12)13/h5-12H,1-4,13-14H2,(H5,25,27,29,31,33)(H5,26,28,30,32,34);2*2-5,7-11H,1H2,(H,12,13)/t;2*2-,3-,4+,5-/m.11/s1
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.3 InChIKey

YZIYKJHYYHPJIB-UUPCJSQJSA-N
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.4 SMILES

C1=CC(=CC=C1N/C(=N/C(=NCCCCCCN=C(/N=C(/NC2=CC=C(C=C2)Cl)\N)N)N)/N)Cl.C(O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(=O)O.C(O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(=O)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C22H30Cl2N10.2C6H12O7
C34H54Cl2N10O14
Computed by PubChem 2.2 (PubChem release 2024.11.20)

2.3 Other Identifiers

2.3.1 CAS

18472-51-0
55-56-1

2.3.2 Deprecated CAS

105791-72-8, 12068-31-4, 124973-71-3, 14007-07-9, 150621-85-5, 151498-43-0, 21293-24-3, 227749-99-7, 230296-52-3, 23289-58-9, 40330-16-3, 452971-25-4, 51365-13-0, 52196-45-9, 52387-19-6, 60042-57-1, 60404-86-6, 82432-16-4, 906339-38-6

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 KEGG ID

2.3.9 Metabolomics Workbench ID

2.3.10 NCI Thesaurus Code

2.3.11 Pharos Ligand ID

2.3.12 RXCUI

2.3.13 Wikidata

2.3.14 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 1,1'-HBCB
  • avagard
  • Chlorhexamed
  • chlorhexidine bigluconate
  • chlorhexidine digluconate
  • chlorhexidine gluconate
  • Corsodyl ICI
  • Curasept ADS 220
  • Dyna-Hex
  • Eludril
  • Gibitan
  • Hexidine
  • Hibiclens
  • Hibident
  • Hibiscrub
  • Hibisol
  • Hibitane
  • Peridex
  • Perio Chip

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
897.8 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Donor Count
Property Value
18
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Acceptor Count
Property Value
16
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Rotatable Bond Count
Property Value
23
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Exact Mass
Property Value
896.3198018 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Monoisotopic Mass
Property Value
896.3198018 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Topological Polar Surface Area
Property Value
454Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Heavy Atom Count
Property Value
60
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
819
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
8
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
2
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
3
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Crystals from methanol; [HSDB]

3.2.2 Color / Form

Crystals from methanol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 371
Solid
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 12th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2012., p. V2: 586

3.2.3 Melting Point

134 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 371

3.2.4 Solubility

800mg/L (at 20 °C)
MERCK INDEX (1996)
MW: 578.38; crystals; decomposes 260-262 °C. Solubility in water at 20 °C: 0.06 g/100 mL /Chlorhexidine dihydrochloride/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 371
Solubility in water at 20 °C: >50% /Chlorhexidine d-digluconate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 371
In water, 800 mg/L at 20 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 371

3.2.5 LogP

0.08
HANSCH,C ET AL. (1995), ionized pH 5
log Kow = 0.080 at pH 5
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 178

3.2.6 Stability / Shelf Life

Stable under ambient warehouse conditions to moisture and simulated sunlight. /Chlorhexidine diacetate/
USEPA/Office of Pesticide Programs; Reregistration Eligibility Decision Document - Chlorhexidine diacetate. EPA738-R-96-025 September 1996. Available from, as of March 11, 2004: https://www.epa.gov/pesticides/reregistration/status.htm
Stable under recommended storage conditions.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html

3.2.7 Dissociation Constants

pKa
10.8 (at 25 °C)
HANSCH,C & LEO,AJ (1985)

3.2.8 Other Experimental Properties

Strong alkaline reaction
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 371
When heated to decomposition, emits very toxic fumes of Cl- and NOX.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 12th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2012., p. V2: 586
MW: 625.6; crystals; mp: 154-155 °C. Neutral reaction. Solubility in water at 20 °C: 1.9 g/100 mL. Aqueous solution decomposes when heated above 70 °C. Soluble in alcohol, glycerol, propylene glycol, polyethylene glycol. /Chlorhexidine diacetate/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 371

3.3 Chemical Classes

Other Uses -> Biocides/Disinfectants

3.3.1 Drugs

3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents, Local; Antibacterial Agents; Disinfectants; Mouthwashes
Human drug -> Discontinued
Human drug -> Prescription
Human drug -> Over-the-counter
Human drug -> Over-the-counter; Discontinued
Human drug -> Prescription; Discontinued
Human drug -> Prescription; Over-the-counter; Discontinued; Active ingredient (CHLORHEXIDINE GLUCONATE)

Antiseptics

Medicines administered to the neonate [c]

3.3.2 Cosmetics

Cosmetic ingredients (Chlorhexidine) -> CIR (Cosmetic Ingredient Review)
Cosmetic ingredients (Chlorhexidine Digluconate) -> CIR (Cosmetic Ingredient Review)
Preservative
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

3.3.3 Fragrances

Fragrance Ingredient (D-​Gluconic acid, compd. with N1,​N14-​bis(4-​chlorophenyl)​-​3,​12-​diimino-​2,​4,​11,​13-​tetraazatetradecaned​iimidamide (2:1)) -> IFRA transparency List

5 Chemical Vendors

6 Drug and Medication Information

6.1 Drug Indication

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. Dental formulations, available by prescription only, include an oral rinse indicated for the treatment of gingivitis 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.

6.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents, Local; Antibacterial Agents; Disinfectants; Mouthwashes

6.3 WHO Essential Medicines

Drug
Drug Classes
Antiseptics
Formulation
Local - Topical - Solution: 5% (digluconate) for dilution
Indication
Chlorhexidine
Drug
Drug Classes
Medicines administered to the neonate [c]
Formulation
(1) Local - Topical - Solution: 7.1% chlorhexidine digluconate (delivering 4% chlorhexidine); (2) Local - Topical - Gel: 7.1% chlorhexidine digluconate (delivering 4% chlorhexidine)
Indication
Omphalitis of newborn

6.4 FDA Approved Drugs

6.5 FDA Orange Book

6.6 FDA National Drug Code Directory

6.7 Drug Labels

Drug and label
Active ingredient and drug
Drug and label
Active ingredient and drug

6.8 Clinical Trials

6.8.1 ClinicalTrials.gov

6.8.2 EU Clinical Trials Register

6.8.3 NIPH Clinical Trials Search of Japan

6.9 Therapeutic Uses

Antiseptic; disinfectant. (Vet): antiseptic; disinfectant.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 371
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. /Chlorhexidine gluconate-topical/
Drug Facts and Comparisons 2013. Wolters Kluwer Health St. Louis, MO 2013, p. 3180
EXPL THER 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.
Nittayananta W et al; Oral Dis. (7): 665-70 (2008)
/EXPTL Therapy:/ Rats were injected with 10 mg/kg azoxymethane sc weekly for 12 weeks to induce colorectal cancers. At 20 weeks, subtotal colectomies were performed on rats with colorectal tumors and without peritoneal implants or liver metastases. At the time of surgery, a cut portion of the tumor was placed in the abdomen for 30 minutes; the rats then randomly received peritoneal irrigation with chlorhexidine, or sterile water (control). Eight weeks postoperatively a necropsy was performed. At that time, obvious and suspected recurrences and the anastomotic area were sampled for histologic evaluation. Significant differences were seen with chlorhexidine vs. water for gross tumor (P=0.05) and microscopic tumor (P<0.05).
Stuntz M et al; Dis Colon Rectum 40 (9): 1058-8 (1997)

6.10 Drug Warnings

For external use only: 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. /Chlorhexidine gluconate-topical/
Drug Facts and Comparisons 2013. Wolters Kluwer Health St. Louis, MO 2013, p. 3180
Sensitivity: Chlorhexidine gluconate should not be used by persons who have a sensitivity to it or its components.
Drug Facts and Comparisons 2013. Wolters Kluwer Health St. Louis, MO 2013, p. 3180
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.
Drug Facts and Comparisons 2013. Wolters Kluwer Health St. Louis, MO 2013, p. 3180
Deafness: Chlorhexidine gluconate has been reported to cause deafness when instilled in the middle ear through perforate ear drums. /Chlorhexidine gluconate-topical/
Drug Facts and Comparisons 2013. Wolters Kluwer Health St. Louis, MO 2013, p. 3180
For more Drug Warnings (Complete) data for CHLORHEXIDINE (8 total), please visit the HSDB record page.

7 Pharmacology and Biochemistry

7.1 Pharmacodynamics

Chlorhexidine is a broad-spectrum antimicrobial with demonstrated activity against both gram-positive and gram-negative bacteria, yeasts, and viruses. Antimicrobial activity is dose-dependent - chlorhexidine is bacteriostatic at lower concentrations (0.02%-0.06%) and bactericidal at higher concentrations (>0.12%). 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. 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. 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. Allergic reactions to chlorhexidine have been associated with the development of anaphylaxis.

7.2 MeSH Pharmacological Classification

Anti-Infective Agents, Local
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. (See all compounds classified as Anti-Infective Agents, Local.)
Dermatologic Agents
Drugs used to treat or prevent skin disorders or for the routine care of skin. (See all compounds classified as Dermatologic Agents.)

7.3 FDA Pharmacological Classification

1 of 15
Non-Proprietary Name
0.12% CHLORHEXIDINE GLUCONATE
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
2 of 15
Non-Proprietary Name
2% CHLORHEXIDINE GLUCONATE SOLUTION
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
3 of 15
Non-Proprietary Name
ANTISEPTIC SKIN CLEANSER
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
4 of 15
Non-Proprietary Name
ANTISEPTIC SURGICAL SCRUB
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
5 of 15
Non-Proprietary Name
CHLORHEXIDINE GLUCONANTE
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
6 of 15
Non-Proprietary Name
CHLORHEXIDINE GLUCONATE
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
7 of 15
Non-Proprietary Name
CHLORHEXIDINE GLUCONATE 0.12% ORAL RINSE
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
8 of 15
Non-Proprietary Name
CHLORHEXIDINE GLUCONATE 2%
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
9 of 15
Non-Proprietary Name
CHLORHEXIDINE GLUCONATE 2% SOLUTION
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
10 of 15
Non-Proprietary Name
CHLORHEXIDINE GLUCONATE 4%
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
11 of 15
Non-Proprietary Name
CHLORHEXIDINE GLUCONATE ORAL RINSE
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
12 of 15
Non-Proprietary Name
CHLORHEXIDINE GLUCONATE SOLUTION 0.75% ANTISEPTIC
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
13 of 15
Non-Proprietary Name
CHLORHEXIDINE GLUCONATE, 0.12% ORAL RINSE
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
14 of 15
Non-Proprietary Name
CHLORHEXIDINE GLUCONATE, 0.12% ORAL RINSE SOLUTION
Pharmacological Classes
Decreased Cell Wall Integrity [PE]
15 of 15
Non-Proprietary Name
SCRUB
Pharmacological Classes
Increased Histamine Release [PE]; Cell-mediated Immunity [PE]; Increased IgG Production [PE]; Glycerol [CS]; Allergens [CS]; Non-Standardized Chemical Allergen [EPC]

7.4 ATC Code

S - Sensory organs

S03 - Ophthalmological and otological preparations

S03A - Antiinfectives

S03AA - Antiinfectives

S03AA04 - Chlorhexidine

S - Sensory organs

S02 - Otologicals

S02A - Antiinfectives

S02AA - Antiinfectives

S02AA09 - Chlorhexidine

R - Respiratory system

R02 - Throat preparations

R02A - Throat preparations

R02AA - Antiseptics

R02AA05 - Chlorhexidine

A - Alimentary tract and metabolism

A01 - Stomatological preparations

A01A - Stomatological preparations

A01AB - Antiinfectives and antiseptics for local oral treatment

A01AB03 - Chlorhexidine

D - Dermatologicals

D08 - Antiseptics and disinfectants

D08A - Antiseptics and disinfectants

D08AC - Biguanides and amidines

D08AC02 - Chlorhexidine

B - Blood and blood forming organs

B05 - Blood substitutes and perfusion solutions

B05C - Irrigating solutions

B05CA - Antiinfectives

B05CA02 - Chlorhexidine

D - Dermatologicals

D09 - Medicated dressings

D09A - Medicated dressings

D09AA - Medicated dressings with antiinfectives

D09AA12 - Chlorhexidine

S - Sensory organs

S01 - Ophthalmologicals

S01A - Antiinfectives

S01AX - Other antiinfectives

S01AX09 - Chlorhexidine

D08AC02

7.5 Absorption, Distribution and Excretion

Absorption
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). Following the insertion of 4 PerioChips in 18 adult patients, no detectable plasma or urine chlorhexidine levels were observed.
Route of Elimination
Excretion of chlorhexidine gluconate occurs almost exclusively via the feces, with less than 1% of an ingested dose excreted in the urine.
34 newborn infants who had been bathed in a standard manner with Hibiscrub were studied to find out whether it was absorbed percutaneously. Low levels of chlorhexidine were found in the blood of all 10 babies sampled by heel prick, and 5 of 24 from whom venous blood was taken. /Chlorhexidine gluconate/
Cowen J et al; Arch Dis Child 54 (5): 379-83 (1979)
Percutaneous absorption of the antimicrobial agent chlorhexidine (labelled with carbon-14) was studied in rats. Less than 5% of the topically applied chlorhexidine was absorbed during a 5-day period. Excretion of absorbed radioactivity occurred mainly in the feces.
Chow CP, et al; Toxicol Lett 1(4): 213-16 (1978)
The percutaneous absorption of chlorhexidine gluconate (chlorhexidine digluconate; Hibitane) through hairless rat skin with or without stratum corneum was studied. 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. /Chlorhexidine gluconate/
Lafforque C et al; Int J Pharm 147: 243-6 (1997)
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.
Middleton JR et al; J Am Vet Med Assoc 222 (12): 1746-9 (2003)

7.6 Metabolism / Metabolites

As chlorhexidine is very poorly absorbed in the gastrointestinal tract, it is unlikely to undergo metabolic conversion to any significant extent.

7.7 Biological Half-Life

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.
Middleton JR et al; J Am Vet Med Assoc 222 (12): 1746-9 (2003)

7.8 Mechanism of Action

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. 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.

8 Use and Manufacturing

8.1 Uses

Cosmetic Ingredient Review Link
CIR ingredient: Chlorhexidine
Cosmetic Ingredient Review Link
Sources/Uses
Chlorhexidine is used in antibacterial soaps and cleansers. [Marks, p. 228-9]
Marks - Marks JG, DeLeo VA. Contact and Occupational Dermatology, 2nd Ed. St. Louis: Mosby, 1997., p. 228-9
Industrial Processes with risk of exposure
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./
National Pesticide Information Retrieval System's Database on Chlorhexidine (55-56-1). Available from, as of October 30, 2014: https://npirspublic.ceris.purdue.edu/ppis/
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/
National Pesticide Information Retrieval System's Database on Chlorhexidine diacetate (56-95-1). Available from, as of October 30, 2014: https://npirspublic.ceris.purdue.edu/ppis/
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/
National Pesticide Information Retrieval System's Database on Chlorhexidine digluconate (18472-51-0). Available from, as of October 30, 2014: https://npirspublic.ceris.purdue.edu/ppis/
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/
National Pesticide Information Retrieval System's Database on Chlorhexidine dihydrochloride (3697-42-5). Available from, as of October 30, 2014: https://npirspublic.ceris.purdue.edu/ppis/
For more Uses (Complete) data for CHLORHEXIDINE (9 total), please visit the HSDB record page.

Use (kg; approx.) in Germany (2009): >1000

Use (kg) in USA (2002): 2660

Consumption (g per capita; approx.) in Germany (2009): 0.0122

Consumption (g per capita) in the USA (2002): 0.00943

Excretion rate: 0.95

Calculated removal (%): 49.6

8.1.1 Use Classification

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Fragrance Ingredients
Cosmetics -> Preservative
S13 | EUCOSMETICS | Combined Inventory of Ingredients Employed in Cosmetic Products (2000) and Revised Inventory (2006) | DOI:10.5281/zenodo.2624118

8.1.2 Household Products

Household & Commercial/Institutional Products

Information on 17 consumer products that contain Chlorhexidine gluconate in the following categories is provided:

• Personal Care

• Pet Care

8.2 Methods of Manufacturing

It can be prepared ... from 1,6-hexamethylenebis(dicyandiamide) and 4-chloroaniline hydrochloride.
Ullmann's Encyclopedia of Industrial Chemistry. 6th ed.Vol 1: Federal Republic of Germany: Wiley-VCH Verlag GmbH & Co. 2003 to Present, p. V16 84 (2003)

8.3 Formulations / Preparations

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.
European Chemicals Bureau; IUCLID Dataset, Chlorhexidine (55-56-1) (2000 CD-ROM edition). Available from, as of March 11, 2003: https://esis.jrc.ec.europa.eu/
Nolvasan Solution (Zoetis, Inc.): Active ingredient: chlorhexidine diacetate 2.0%. /Chlorhexidine diacetate/
National Pesticide Information Retrieval System's Database on Chlorhexidine diacetate (56-95-1). Available from, as of October 30, 2014: https://npirspublic.ceris.purdue.edu/ppis/
Fort Dodge Nolvasan S (Zoetis, Inc.): Active ingredient: chlorhexidine diacetate 2.0%. /Chlorhexidine diacetate/
National Pesticide Information Retrieval System's Database on Chlorhexidine diacetate (56-95-1). Available from, as of October 30, 2014: https://npirspublic.ceris.purdue.edu/ppis/
Chlorhexidine Diacetate (Zoetis, Inc.): Active ingredient: chlorhexidine diacetate 99.3%. /Chlorhexidine diacetate/
National Pesticide Information Retrieval System's Database on Chlorhexidine diacetate (56-95-1). Available from, as of October 30, 2014: https://npirspublic.ceris.purdue.edu/ppis/
For more Formulations/Preparations (Complete) data for CHLORHEXIDINE (9 total), please visit the HSDB record page.

8.4 U.S. Production

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.
US EPA; Non-Confidential 2006 Inventory Update Reporting. National Chemical Information. 2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino- (55-56-1). Available from, as of November 5, 2014: https://cfpub.epa.gov/iursearch/index.cfm

8.5 General Manufacturing Information

EPA TSCA Commercial Activity Status
D-Gluconic acid, compd. with N1,N14-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide (2:1): ACTIVE
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).
Guthner T et al; Guanidine and Derivatives. Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (1999-2014). New York, NY: John Wiley & Sons. Online Posting Nov 6, 2014: 15 Jul 2006

9 Identification

9.1 Analytic Laboratory Methods

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.
Cropper E et al; J. Soc. Cosmet. Chem. 26 (7): 355-373 (1975)

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

1 of 5
View All
Note
Pictograms displayed are for 99.6% (250 of 251) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 0.4% (1 of 251) of reports.
Pictogram(s)
Corrosive
Irritant
Environmental Hazard
Signal
Danger
GHS Hazard Statements

H302 (19.9%): Harmful if swallowed [Warning Acute toxicity, oral]

H318 (68.5%): Causes serious eye damage [Danger Serious eye damage/eye irritation]

H400 (87.6%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

H410 (87.3%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P264, P264+P265, P270, P273, P280, P301+P317, P305+P354+P338, P317, P330, P391, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 251 reports by companies from 19 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 1 of 251 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 18 notifications provided by 250 of 251 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.

10.1.2 Hazard Classes and Categories

Acute Tox. 3 (19.9%)

Eye Dam. 1 (68.5%)

Aquatic Acute 1 (87.6%)

Aquatic Chronic 1 (87.3%)

Acute Tox. 4 (29.2%)

Skin Irrit. 2 (64.2%)

Eye Dam. 1 (34.2%)

Eye Irrit. 2 (66.7%)

Resp. Sens. 1 (35%)

STOT SE 3 (37.5%)

STOT RE 2 (29.2%)

Aquatic Acute 1 (91.7%)

Aquatic Chronic 1 (93.3%)

10.1.3 Hazards Summary

Chlorhexidine is rarely sensitizing. In one series, 0.1% of photosensitive patients had positive photo patch tests results for chlorhexidine. The 1% concentration may cause irritant effects. [Marks, p. 228-9] Immunologic contact urticaria has been reported; [Kanerva, p. 219] Occupational asthma reported in two nurses; [Malo]
Marks - Marks JG, DeLeo VA. Contact and Occupational Dermatology, 2nd Ed. St. Louis: Mosby, 1997., p. 228-9
Kanerva - Rustemeyer L, Elsner P, John SM, Maibach HI (eds). Kanerva's Occupational Dermatology, 2nd Ed. Berlin: Springer-Verlag, 2012., p. 219

10.1.4 Skin, Eye, and Respiratory Irritations

Causes moderate eye irritation. /0.01% Chlorhexidine diacetate, from Cougar product label/
U.S. Environmental Protection Agency/Office of Pesticide Program's Chemical Ingredients Database on Chlorhexidine diacetate (56-95-1). Available from, as of March 11, 2004: https://npirspublic.ceris.purdue.edu/ppis/
Irritating to eye and mucous membranes. /Nolvasan-S, Chlorhexidine diacetate/
AHFSS, CA Dept of Food and Agriculture; Biosecurity-Selection and Use of Surface Disinfectants (June 2002). Available from, as of March 11, 2003: https://www.cdfa.ca.gov/ahfss/ah/pdfs/biosecurity_surface_disinfect_b4.pdf
Chlorhexidine diacetate ...is highly acutely toxic when applied to the eye. /Chlorhexidine diacetate/
USEPA/Office of Pesticide Programs; Reregistration Eligibility Decision Facts - Chlorhexidine diacetate. EPA-738-F-96-025 September 1996. Available from, as of March 11, 2004: https://www.epa.gov/pesticides/reregistration/status.htm

10.2 Fire Fighting

10.2.1 Fire Fighting Procedures

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html
Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html

10.2.2 Firefighting Hazards

Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx), hydrogen chloride gas.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html

10.3 Accidental Release Measures

10.3.1 Cleanup Methods

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html

10.3.2 Disposal Methods

SRP: 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.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html

10.3.3 Preventive Measures

SRP: 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.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html
Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html
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.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html
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. Ensure that the local ventilation moves the contaminant away from the worker.

10.4 Exposure Control and Personal Protection

10.4.1 Personal Protective Equipment (PPE)

Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html
Skin protection: Handle with gloves.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html
Body Protection: Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html
Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html

10.5 Stability and Reactivity

10.5.1 Hazardous Reactivities and Incompatibilities

Strong alkaline reaction.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 371
Incompatible materials: Strong oxidizing agents.
Sigma-Aldrich; Material Safety Data Sheet for Chlorhexidine. Product Number: 282227, Version 5.3 (Revision Date 06/30/2014). Available from, as of October 10, 2014: https://www.sigmaaldrich.com/safety-center.html

10.6 Regulatory Information

The Australian Inventory of Industrial Chemicals
Chemical: D-Gluconic acid, compd. with N1,N14-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide (2:1)
REACH Registered Substance
REACH Registered Substance
New Zealand EPA Inventory of Chemical Status
Chlorhexidine gluconate: Does not have an individual approval but may be used under an appropriate group standard
New Zealand EPA Inventory of Chemical Status
Chlorhexidine: Does not have an individual approval but may be used under an appropriate group standard

10.6.1 FIFRA Requirements

Based on the reviews of the generic data for the active ingredient chlorhexidine diacetate, the Agency has sufficient information on the health effects of chlorhexidine diacetate and on its potential for causing adverse effects in fish and wildlife and the environment. The Agency has determined that chlorhexidine diacetate products, labeled and used as specified in this Reregistration Eligibility Decision, will not pose unreasonable risks or adverse effects to humans or the environment. Therefore, the Agency concludes that products containing chlorhexidine diacetate for all uses are eligible for reregistration. /Chlorhexidine diacetate/
USEPA/Office of Prevention, Pesticides and Toxic Substances; Reregistration Eligibility Decision Document for Chlorhexidine diacetate p.17 EPA 738-R-96-025 (September 1996). Available from, as of November 4, 2014: https://www.epa.gov/pesticides/reregistration/status.htm
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/
United States Environmental Protection Agency/ Prevention, Pesticides and Toxic Substances; Status of Pesticides in Registration, Reregistration, and Special Review. (1998) EPA 738-R-98-002, p. 242
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/
United States Environmental Protection Agency/ Prevention, Pesticides and Toxic Substances; Status of Pesticides in Registration, Reregistration, and Special Review. (1998) EPA 738-R-98-002, p. 242
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/
United States Environmental Protection Agency/ Prevention, Pesticides and Toxic Substances; Status of Pesticides in Registration, Reregistration, and Special Review. (1998) EPA 738-R-98-002, p. 242

10.6.2 FDA Requirements

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. /Chlorhexidine gluconate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of February 10, 2004: https://www.fda.gov/cder/ob/
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.
21 CFR 524.402 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of October 27, 2014: https://www.ecfr.gov
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.
21 CFR 529.400 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of October 27, 2014: https://www.ecfr.gov
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.
21 CFR 556.120 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of October 27, 2014: https://www.ecfr.gov

10.7 Other Safety Information

Chemical Assessment
IMAP assessments - Chlorhexidine: Human health tier II assessment

10.7.1 Special Reports

USEPA/Office of Prevention, Pesticides and Toxic Substances; Reregistration Eligibility Decision Document - Chlorhexidine Diacetate, EPA 738-R-96-025 (September 1996). The RED summarizes the risk assessment conclusions and outlines any risk reduction measures necessary for the pesticide to continue to be registered in the U.S.[Available from, as of November 4, 2014: http://www.epa.gov/pesticides/reregistration/status.htm]

11 Toxicity

11.1 Toxicological Information

11.1.1 Toxicity Summary

IDENTIFICATION AND USE: 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.

11.1.2 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Chlorhexidine has been used vaginally or topically on the abdomen or perineum prior to delivery to prevent infection. No toxicity has been reported in breastfed infants and it has clearly less toxicity compared to povidone-iodine in these situations. Topical application of chlorhexidine to the breast before and after nursing did not appear to adversely affect the breastfed infants in one study. Use of chlorhexidine oral rinse by a nursing mother is unlikely to adversely affect her infant.

◉ Effects in Breastfed Infants

A group of investigators in Belgium reviewed the results of infant thyrotropin levels on day 5 postpartum in 4745 newborn infants delivered over a 2-year period at their hospital. Infants were divided among those whose mothers had iodine overload (n = 3086) from topical povidone-iodine 10% solution during labor and delivery and those whose mothers had no iodine overload (n = 1659). Mothers had povidone-iodine applied either as a single application to 900 square cm for epidural anesthesia or 3 applications to the entire abdominal wall for cesarean section. Breastfed infants whose mothers had iodine overload had a greater risk for having elevated thyrotropin levels and requiring recall for retesting (3.2% with cesarean section and 2.7% with epidural anesthesia) compared to those who did not (0.1%). Bottle-fed infants were affected much less than breastfed infants. After replacing povidone-iodine with chlorhexidine 0.5% in 70% isopropanol for disinfection for 6 months, 1178 infants that were delivered at this institution had no increased rate of elevations in thyroid function tests and a reduced rate of recalls in breastfed infants.

In a study of mothers in Spain who received 10% povidone-iodine (n = 21) or chlorhexidine (n = 13) topically to the perineum starting immediately before the final stage of labor and daily postpartum to the episiotomy, no differences in thyrotropin, thyroxine or free thyroxine was found among their breastfed infants at day 5 to 7 postpartum.

Studies in Africa have used chlorhexidine vaginally prior to delivery in an attempt to reduce the frequency of mother-to-child transmission (MTCT) of HIV. In one, cotton soaked in 0.25% chlorhexidine solution was used to swab the vaginal walls every 4 hours from admission into labor until delivery in 4078 women. The other study used 120 mL of either 0.2% or 0.4% chlorhexidine solution as a vaginal lavage every 3 hours from admission to labor until delivery in 309 women. The average number of lavages was 2.1 (range 1 to 11). Chlorhexidine 0.25% swabs reduced MTCT in patients whose membranes ruptured more than 4 hours before delivery, but not in other women. Vaginal lavage showed a statistically nonsignificant trend towards reduction of MTCT, with the 0.4% greater than the 0.2%. Almost all of the infants in these studies were breastfed. No adverse events were reported in the infants, but follow-up related primarily to infant mortality and HIV status rather than effects of chlorhexidine.

◉ Effects on Lactation and Breastmilk

A randomized study compared 0.2% chlorhexidine in alcohol to distilled water as a spray to the breast in 200 mothers who were nursing newborns. The mothers sprayed their breasts with the liquid before and after each feeding. Mothers and infants were assessed at discharge and weekly thereafter. Discomfort and nipple trauma were less frequent in the chlorhexidine group than in the placebo group, particularly at the first assessment. Although skin flora on the breasts of the treated mothers was reduced, there was no difference in the frequency of mastitis between the treated and placebo groups. No obvious side effects occurred in the breastfed infants and there were no differences in the rates of oral thrush in infants between the treatments. A systematic review concluded that this practice is not justified based on current evidence.

11.1.3 Adverse Effects

Dermatotoxin - PACD (photoallergic contact dermatitis).

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

Asthma - Reversible bronchoconstriction (narrowing of bronchioles) initiated by the inhalation of irritating or allergenic agents.

11.1.4 Acute Effects

11.1.5 Interactions

Chlorhexidine increases the activity of itraconazole against Candida isolates; itraconazole-chlorhexidine combinations show synergistic activity in culture media.
Simonetti N et al; Drugs Exp Clin Res 14 (1): 19-23 (1988)

11.1.6 Antidote and Emergency Treatment

1. If a highly concentrated solution is ingested, manage as a caustic ingestion ... , without gastrointestinal decontamination.
U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Roberts, J.R., Reigart, J.R. Recognition and Management of Pesticide Poisonings. 6th ed. 2013. EPA Document No. EPA 735K13001, and available in electronic format at: https://www2.epa.gov/pesticide-worker-safety, p. 203
2. Liver injury panel should be performed with large ingestions.
U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Roberts, J.R., Reigart, J.R. Recognition and Management of Pesticide Poisonings. 6th ed. 2013. EPA Document No. EPA 735K13001, and available in electronic format at: https://www2.epa.gov/pesticide-worker-safety, p. 203
If a high concentration solution is in contact with the eyes, wash eyes profusely and examine the corneas carefully. If burns have occurred, obtain ophthalmologic care.
U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Roberts, J.R., Reigart, J.R. Recognition and Management of Pesticide Poisonings. 6th ed. 2013. EPA Document No. EPA 735K13001, and available in electronic format at: https://www2.epa.gov/pesticide-worker-safety, p. 203
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160
For more Antidote and Emergency Treatment (Complete) data for CHLORHEXIDINE (6 total), please visit the HSDB record page.

11.1.7 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ Chlorhexidine diacetate ...is highly acutely toxic when applied to the eye. /Chlorhexidine diacetate/
USEPA/Office of Pesticide Programs; Reregistration Eligibility Decision Facts - Chlorhexidine diacetate. EPA-738-F-96-025 September 1996. Available from, as of March 11, 2004: https://www.epa.gov/pesticides/reregistration/status.htm
/HUMAN EXPOSURE STUDIES/ To evaluate the efficacy of chlorhexidine solution in the treatment of patients with Acanthamoeba keratitis. Prospective nonrandomized study. Five patients infected with culture-proven Acanthamoeba keratitis. Chlorhexidine solution was used hourly on six eyes and gradually reduced to four times a day after 1 month. Follow-up ranged from 1 to 10 months (mean, 4 months). Severity of symptoms and signs, time for healing, and final visual acuity. Clinical results in four patients showed improved visual acuity, with a rapid recovery within 1 wk. No adverse drug reaction was encountered, but one patient with a perforated ulcer developed glaucoma. 83% of 6 eyes were medically cured with chlorhexidine and recovered visual acuity 6/18 or better. Four of five patients improved within 3 weeks, with resolution of infiltration and healing of epithelial defects. By 2 to 3 weeks, visual acuity 6/18 or better had improved in four (66.7%) of six eyes and recovered 6/6 in two eyes (33.3%). Bacterial coinfection occurred in one eye. Chlorhexidine dramatically hastened clinical improvement in all eyes and is a successful medical therapy that has excellent results in patients who are diagnosed early.
Kosrirukvongs P et al; Ophthalmology 106 (4): 798-802 (1999)
/HUMAN EXPOSURE STUDIES/ Skin reactions to chlorhexidine-acetate and chlorhexidine-gluconate were tested among eczema patients. Subjects were tested with 1% chlorhexidine-gluconate and 1% chlorhexidine-acetate by patch test. The patches were applied for 48 hours and read at 72 hours. Subjects with a positive reaction at the initial testing were retested 1 month later. 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. A use test performed on these 29 patients resulted in all of them developing a dermatitis with one or both of the chlorhexidine solutions. Those patients with leg eczema or leg ulcers appeared to be particularly at risk. The /study/ conclude that patients with eczema, and especially those with leg ulcers or leg eczema, are especially prone to chlorhexidine allergies.
Andersen BL et al; Contact Dermatitis 13 (5): 307-9 (1985)
/HUMAN EXPOSURE STUDIES/ In Denmark, chlorhexidine is the standard disinfectant in most hospitals and health care workers are repeatedly exposed to it. The aim of this study was to establish whether there is a risk of sensitization and allergy to chlorhexidine from this type of exposure. Two hundred and forty-eight doctors, nurses and auxiliary staff were invited to participate in the study. One hundred and four individuals took part in the full study including skin tests and a questionnaire and a further 74 individuals filled in the questionnaire giving a total of 178 questionnaires (72%). Patch tests with chlorhexidine gluconate 1% and chlorhexidine acetate 1% were performed looking for type IV (delayed type) allergy. A prick test with chlorhexidine gluconate 0.5% and an intradermal test with chlorhexidine 0.0002% were performed looking for type I (immediate type) allergy. There were no positive tests in any of the 104 individuals tested (99% confidence interval 0-4.9%). There was a predominance of females in both groups and the overall median age was 42 years (28-63). No one in the group not tested reported to have a verified or suspected allergy to chlorhexidine. This ...study to examine the risk of type I and type IV allergy to chlorhexidine in health care workers with daily exposure to chlorhexidine did not identify allergies to chlorhexidine in any of the 104 individuals tested or in the additional 74 individuals who completed the questionnaire.
Gavrey LH et al; Acta Anaesthesiol Scand 47 (6): 720-4 (2003)
For more Human Toxicity Excerpts (Complete) data for CHLORHEXIDINE (22 total), please visit the HSDB record page.

11.1.8 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ One-tenth gram of chlorhexidine acetate, purity 99.50%, was placed in the conjunctival sac of one eye of each of 6 New Zealand White rabbits. Eyes were examined at 1, 24, 48 and 72 hours and at 4 and 7 days after dose administration. Test animals suffered severe ocular irritation with chlorhexidine acetate treatment , which resulted in their sacrifice for humane reasons on day 7 of the study. /Chlorhexidine acetate/
California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summaries. Available from: https://www.cdpr.ca.gov/docs/toxsums/toxsumlist.htm on Chlorhexidine diacetate as of March 11, 2004.
/LABORATORY ANIMALS: Acute Exposure/ One-half gram (0.5 g) of chlorhexidine acetate, purity 99.5%, moistened with 0.5-mL physiological saline, was applied topically to the shaved area of 6 New Zealand White rabbits, 3/sex, for 4 hours. A gauze was applied after dosing to protect the treated area for the 4 hours, after which the gauze removed and the treated area cleaned. Dermal irritation was evaluated at 0.5, 24, 48 and 72 hours after removal of the protective gauze. No dermal irritation was reported up to 72 hours following test article treatment for any of the test animals. /Chlorhexidine acetate/
California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summaries. Available from: https://www.cdpr.ca.gov/docs/toxsums/toxsumlist.htm on Chlorhexidine diacetate as of March 11, 2004.
/LABORATORY ANIMALS: Acute Exposure/ Chlorhexidine Acetate, 99.5%, Lot 3-P, was administered as a single dose by gavage at 2,000, 2,646 or 3,500 mg/kg to 5 Sprague-Dawley rats/sex/group. Animals were observed for 15 days for treatment-related effects and mortality. Clinical observation and necropsy indicate treatment-related effects at all doses. /Chlorhexidine acetate/
California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summaries. Available from: https://www.cdpr.ca.gov/docs/toxsums/toxsumlist.htm on Chlorhexidine diacetate as of March 11, 2004.
/LABORATORY ANIMALS: Acute Exposure/ Chlorhexidine Acetate, purity 99.50%, was applied topically for a period of 24 hours at 2,000 mg/kg to 5 New Zealand White rabbits/sex. The material was moistened with saline, covered with gauze and occluded. Animals were observed for a period of 15 days. Clinical observation indicated treatment-related effects of dry skin at the application site. Test article caused dermal irritation (erythema, edema and dry skin). All animals survived to terminal sacrifice. /Chlorhexidine acetate/
California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summaries. Available from: https://www.cdpr.ca.gov/docs/toxsums/toxsumlist.htm on Chlorhexidine diacetate as of March 11, 2004.
For more Non-Human Toxicity Excerpts (Complete) data for CHLORHEXIDINE (18 total), please visit the HSDB record page.

11.1.9 Non-Human Toxicity Values

LD50 Rat oral 5,000 mg/kg
European Chemicals Bureau; IUCLID Dataset, Chlorhexidine (55-56-1) (2000 CD-ROM edition). Available from, as of March 11, 2003: https://esis.jrc.ec.europa.eu/
LD50 Rat (male) oral 1710 mg/kg /Chlorhexidine diacetate/
USEPA/Office of Pesticide Programs; Reregistration Eligibility Decision Document - Chlorhexidine diacetate. EPA738-R-96-025 September 1996. Available from, as of March 11, 2004: https://www.epa.gov/pesticides/reregistration/status.htm
LD50 Rat (female) oral 1180 mg/kg /Chlorhexidine diacetate/
USEPA/Office of Pesticide Programs; Reregistration Eligibility Decision Document - Chlorhexidine diacetate. EPA738-R-96-025 September 1996. Available from, as of March 11, 2004: https://www.epa.gov/pesticides/reregistration/status.htm
LD50 Rabbit dermal >2000 mg/kg /Chlorhexidine diacetate/
USEPA/Office of Pesticide Programs; Reregistration Eligibility Decision Document - Chlorhexidine diacetate. EPA738-R-96-025 September 1996. Available from, as of March 11, 2004: https://www.epa.gov/pesticides/reregistration/status.htm
For more Non-Human Toxicity Values (Complete) data for CHLORHEXIDINE (6 total), please visit the HSDB record page.

11.1.10 Ongoing Test Status

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of November 5, 2014: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=55-56-1]

11.1.11 Protein Binding

Chlorhexidine is known to bind albumin in both serum and saliva, though the extent of this binding is unclear.

11.2 Ecological Information

11.2.1 Ecotoxicity Values

LC50; Species: /Oncorhynchus mykiss/ (Rainbow trout); Concentration: 1.3 ug/L for 96 hr /Conditions of bioassay not specified in source examined/
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. 792
LC50; Species: Pteronarcys /stonefly/; Concentration: 0.5 ug/L for 48 hr /Conditions of bioassay not specified in source examined/
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. 792
LC50; Species: Daphnia magna (Water flea); Concentration: 250 ug/L for 48 hr /Conditions of bioassay not specified in source examined/
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. 792
LC50; Species: Daphnia magna /(Water flea)/; Concentration: 740 ug/L for 25 hr /Conditions of bioassay not specified in source examined/
Verschueren, K. Handbook of Environmental Data on Organic Chemicals. Volumes 1-2. 4th ed. John Wiley & Sons. New York, NY. 2001, p. 792
For more Ecotoxicity Values (Complete) data for CHLORHEXIDINE (10 total), please visit the HSDB record page.

11.2.2 Environmental Fate / Exposure Summary

Chlorhexidine's production and use primarily as its salts in disinfectants, cosmetics, and pharmaceutical products may result in its release to the environment through various waste streams. Chlorhexidine diacetate salt's use as a disinfectant to control bacteria on farms, egg handling and packaging equipment, meat and poultry processing plants, and certain viruses in veterinary settings may result in chlorhexidine's direct release to the environment. If released to air, an estimated vapor pressure of 2.0X10-14 mm Hg at 25 °C indicates chlorhexidine will exist solely in the particulate phase in the atmosphere. Particulate-phase chlorhexidine will be removed from the atmosphere by wet and dry deposition. Irradiation (lambda >290 nm) of chlorhexidine sorbed to silica gel resulted in 20% degradation after 17 hours. However, this chemical is expected to exist in the particulate phase in the ambient atmosphere and, therefore, photo-degradation is not expected to be an important fate process. If released to soil, chlorhexidine is expected to have no mobility based upon an estimated Koc of 8.5X10+5. Values of pKa 7.63, 9.92, 8.22 and 10.52, indicate that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the compound exists as an cation and cations do not volatilize. Chlorhexidine is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Using the OECD Minimal test, chlorhexidine, present at 12 mg/L, achieved 0% degradation after 3 weeks in soil extract inoculum indicating that biodegradation is not expected to be an important fate process in soil. If released into water, chlorhexidine is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Using the Closed Bottle test, chlorhexidine, present at 5.35 ppm, resulted in 0% COD after 28 days using an activated sludge inoculum, indicating that biodegradation is not expected to be an important fate process in water. The pKa values indicate chlorhexidine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to chlorhexidine may occur through inhalation and dermal contact with this compound at workplaces where chlorhexidine is produced or used. Use data indicate that the general population may be exposed to chlorhexidine via oral and dermal contact with consumer products containing this compound. (SRC)

11.2.3 Artificial Pollution Sources

Chlorhexidine's production and use primarily as its salts in disinfectants, cosmetics, and pharmaceutical products(1) may result in its release to the environment through various waste streams(SRC). Chlorhexidine diacetate salt's use as a disinfectant to control bacteria on farms, egg handling and packaging equipment, meat and poultry processing plants, and certain viruses in veterinary settings(2) may result in chlorhexidine's direct release to the environment(SRC).
(1) Guenthener T et al; Guanidine and Derivatives. Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (1999-2014). New York, NY: John Wiley & Sons. Online Posting Nov 6, 2014: 15 Jul 2006
(2) USEPA/OPPTS; Reregistration Eligibility Decisions (REDs) Database on Chlorhexidine Derivatives. EPA738-R-96-025. Sept 1996. Available from, as of Nov 6, 2014: https://www.epa.gov/pesticides/reregistration/status.htm

11.2.4 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 8.5X10+5(SRC), determined from a structure estimation method(2), indicates that chlorhexidine is expected to be immobile in soil(SRC). Values of pKa 7.63, 9.92, 8.22 and 10.52(3), indicate that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Chlorhexidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.0X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Using the OECD Minimal test, chlorhexidine, present at 12 mg/L, achieved 0% degradation after 3 weeks in soil extract inoculum(5), indicating that biodegradation is not expected to be an important fate process in soil(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 4, 2014: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) ChemSpider; Chlorhexidine. (55-56-1). London, UK: Royal Chemical Society. Available from, as of Nov 6, 2014: https://www.chemspider.com/Search.aspx
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Richardson ML, Bowron JM; Environment J Pharm Pharmacol 37: 1-12 (1985)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 8.5X10+5(SRC), determined from a structure estimation method(2), indicates that chlorhexidine is expected to adsorb to suspended solids and sediment(SRC). Values of pKa 7.63, 9.92, 8.22 and 10.52(5) indicate chlorhexidine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow of 0.5(7) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Using the Closed Bottle test, chlorhexidine, present at 5.35 ppm, resulted in 0% COD after 28 days using an activated sludge inoculum(8), indicating that biodegradation is not expected to be an important fate process in water(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 4, 2014: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)
(4) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(5) ChemSpider; Chlorhexidine. (55-56-1). London, UK: Royal Chemical Society. Available from, as of Nov 6, 2014: https://www.chemspider.com/Search.aspx
(6) Franke C et al; Chemosphere 29: 1501-14 (1994)
(7) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 178 (1995)
(8) Dewaart J, Vandermost MM; Int Biodetermination 22: 113-20 (1986)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), chlorhexidine, which has an estimated vapor pressure of 2.0X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase chlorhexidine may be removed from the air by wet and dry deposition(SRC). Irradiation (lambda >290 nm) of chlorhexidine sorbed to silica gel resulted in 20% degradation after 17 hours(3). However, this chemical is expected to exist in the particulate phase in the ambient atmosphere and, therefore, photo-degradation is not expected to be an important fate process(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of November 5, 2014: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Freitag D et al; Chemosphere 14: 1589-616 (1985)

11.2.5 Environmental Biodegradation

AEROBIC: Chlorhexidine is classified as non-biodegradable(1). Under aerobic conditions chlorhexidine, present at 12 mg/L in a mineral salts solution, achieved 0% degradation after 3 weeks in soil extract inoculum using the OECD Minimal test; yet, achieved 60-100% degradation after 3 weeks using a OECD continuous flow synthetic Organic-Medium test with adapted sludge inoculum(2). Chlorhexidine, present at 5.35 ppm, resulted in 0% COD after 28 days using an activated sludge inoculum at 1.5 mg/L in the Closed Bottle test(3). Chlorhexidine, present at 0.05 ppm, resulted in 0.1% CO2 evolution, 94.3% non-extractable residues, and 0.2% volatilization after 5 days using an activated sludge inoculum(4).
(1) Richardson ML, Bowron JM; Environment J Pharm Pharmacol 37: 1-12 (1985)
(2) Voets JP et al; J Appl Bacteriol 40: 67-72 (1976)
(3) Dewaart J, Vandermost MM; Int Biodetermination 22: 113-20 (1986)
(4) Freitag D et al; Ecotox Environ Saf 6: 60-81 (1982)
ANAEROBIC: Under anaerobic conditions, chlorhexidine, present at 12 mg/L in a mineral salts solution, achieved 0% degradation after 3 weeks in 1.0 mL soil extract inoculum, using both an OECD Minimal test and an OECD Organic-Medium test(1).
(1) Voets JP et al; J Appl Bacteriol 40: 67-72 (1976)

11.2.6 Environmental Abiotic Degradation

Irradiation (lambda >290 nm) of chlorhexidine sorbed to silica gel resulted in 20% degradation after 17 hours(1). However, this chemical is expected to exist in the particulate phase in the ambient atmosphere and, therefore, photo-degradation is not expected to be an important fate process(SRC). This substance lacks common hydrolyzable functional groups and is not expected to undergo hydrolysis under environmental conditions(2). Chlorhexidine however has been reported to hydrolyze into 4-chloroaniline(3). According to an OECD guideline study using chlorhexidine dihydrochloride, less than 10% hydrolysis occurred after 5 days. A half life of greater than 1 year at 25 °C and pH 7 was reported(4). This data suggests that chlorhexidine hydrolysis is not an important fate process(SRC).
(1) Freitag D et al; Chemosphere 14: 1589-616(1985)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)
(3) Richardson ML, Bowron JM; J Pharm Pharmacol 37: 1-12 (1985)
(4) European Chemicals Agency; ECHA 2014 Eurpoean Chemicals Agency. Registered Substances. Chlorhexidine. Available from, as of Nov 4, 2014: https://www.echa.europa.eu/web/guest/information-on-chemicals/registered-substances

11.2.7 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for chlorhexidine(SRC), using a log Kow of 0.08(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low. Golden ide fish (Leuciscus idus melanotus) exposed to 0.05 ng/L chlorhexidine for 3 days resulted in a bioaccumulation factor (concentration of chemical in fish/concentration of chemical in water ug/g) of 40(4), which indicates a low bioconcentration potential(SRC).
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 178 (1995)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 4, 2014: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm/
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)
(4) Freitag D et al; Chemosphere 14: 1589-616 (1985)

11.2.8 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of chlorhexidine can be estimated to be 8.5X10+5(SRC). According to a classification scheme(2), this estimated Koc value suggests that chlorhexidine is expected to be immobile in soil. Values for pKa are 7.63, 9.92, 8.22 and 10.52(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 6, 2014: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Swann RL et al; Res Rev 85: 17-28 (1983)
(3) ChemSpider; Chlorhexidine. (55-56-1). London, UK: Royal Chemical Society. Available from, as of Nov 6, 2014: https://www.chemspider.com/Search.aspx
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

11.2.9 Volatilization from Water / Soil

Values for pKa of 7.63, 9.92, 8.22 and 10.52(1) indicate that chlorhexidine will exist almost entirely in the cation form at environmental relevant pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). Chlorhexidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.0X10-14 mm Hg(2).
(1) ChemSpider; Chlorhexidine. (55-56-1). London, UK: Royal Chemical Society. Available from, as of Nov 6, 2014: https://www.chemspider.com/Search.aspx
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 4, 2014: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

11.2.10 Environmental Water Concentrations

No reports of surface water or ground water monitoring studies that included chlorhexidine were found in searches of the United States Geological Survey (USGS) online National Water Quality Assessment Data Warehouse (NAWQA) database, the EPA publication, EPA Pesticides in Ground Water, A Compilation of Monitoring Studies 1971-1991 National Summary(1).
(1) USEPA/OPPTS; Reregistration Eligibility Decisions (REDs) Database on Chlorhexidine derivs /chlorhexidine diacetate/ (CAS No. 56-95-1) Available from, as of Nov 5,2014: https://www.epa.gov/pesticides/reregistration/status.htm

11.2.11 Milk Concentrations

EXPERIMENTAL: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of the long elimination half-life of chlorhexidine in milk from treated mammary gland quarters, the lack of human dietary exposure data to suggest a food tolerance for chlorhexidine in food products, and the Food and Drug Administration's published zero tolerance for chlorhexidine in uncooked edible calf tissues, we do not recommend extralabel use of chlorhexidine suspension as a treatment to stop lactation in mastitic mammary gland quarters of cows.
Middleton JR et al; J Am Vet Med Assoc 222 (12): 1746-9 (2003)

11.2.12 Probable Routes of Human Exposure

NIOSH (NOES Survey 1981-1983) has statistically estimated that 32 workers (32 of these were female) were potentially exposed to chlorhexidine in the US(1). The NOES Survey does not include farm workers.Occupational exposure to chlorhexidine may occur through inhalation and dermal contact with this compound at workplaces where chlorhexidine is produced or used. Use data indicate that the general population may be exposed to chlorhexidine via oral and dermal contact with consumer products containing this compound(SRC).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from, as of Nov 6, 2014: https://www.cdc.gov/noes/

12 Associated Disorders and Diseases

Associated Occupational Diseases with Exposure to the Compound

Asthma, occupational [Category: Airway Disease]

Contact urticaria [Category: Skin Disease]

Contact dermatitis, allergic [Category: Skin Disease]

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Chemical Co-Occurrences in Literature

13.4 Chemical-Gene Co-Occurrences in Literature

13.5 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 FDA Orange Book Patents

14.3 Chemical Co-Occurrences in Patents

14.4 Chemical-Disease Co-Occurrences in Patents

14.5 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Chemical-Target Interactions

15.2 Drug-Drug Interactions

15.3 Drug-Food Interactions

Take separate from meals. May affect the taste of food and beverages. Avoid eating or drinking for 30 minutes following use.

16 Biological Test Results

16.1 BioAssay Results

17 Classification

17.1 MeSH Tree

17.2 NCI Thesaurus Tree

17.3 ChEBI Ontology

17.4 KEGG: Drug

17.5 KEGG: USP

17.6 KEGG: ATC

17.7 KEGG: JP15

17.8 KEGG: Risk Category of Japanese OTC Drugs

17.9 KEGG: OTC drugs

17.10 KEGG: Animal Drugs

17.11 WHO ATC Classification System

17.12 ChemIDplus

17.13 UN GHS Classification

17.14 NORMAN Suspect List Exchange Classification

17.15 Consumer Product Information Database Classification

17.16 EPA TSCA and CDR Classification

17.17 FDA Drug Type and Pharmacologic Classification

18 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    D-Gluconic acid, compd. with N1,N14-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide (2:1)
    https://services.industrialchemicals.gov.au/search-assessments/
    D-Gluconic acid, compd. with N1,N14-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide (2:1)
    https://services.industrialchemicals.gov.au/search-inventory/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  4. EPA Chemicals under the TSCA
    D-Gluconic acid, compd. with N1,N14-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide (2:1)
    https://www.epa.gov/chemicals-under-tsca
    EPA TSCA Classification
    https://www.epa.gov/tsca-inventory
  5. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    D-gluconic acid, compound with N,N''-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediamidine (2:1)
    https://chem.echa.europa.eu/100.038.489
    D-gluconic acid, compound with N,N''-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediamidine (2:1) (EC: 242-354-0)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/58812
  6. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  7. Hazardous Substances Data Bank (HSDB)
  8. International Fragrance Association (IFRA)
    LICENSE
    (c) The International Fragrance Association, 2007-2021. All rights reserved.
    https://ifrafragrance.org/links/copyright
    D-​Gluconic acid, compd. with N1,​N14-​bis(4-​chlorophenyl)​-​3,​12-​diimino-​2,​4,​11,​13-​tetraazatetradecaned​iimidamide (2:1)
    https://ifrafragrance.org/priorities/ingredients/ifra-transparency-list
  9. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  10. ChEBI
  11. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  12. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  13. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  14. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  15. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  16. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  17. Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
    LICENSE
    Copyright (c) 2022 Haz-Map(R). All rights reserved. Unless otherwise indicated, all materials from Haz-Map are copyrighted by Haz-Map(R). No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://haz-map.com/About
  18. Consumer Product Information Database (CPID)
    LICENSE
    Copyright (c) 2024 DeLima Associates. All rights reserved. Unless otherwise indicated, all materials from CPID are copyrighted by DeLima Associates. No part of these materials, either text or image may be used for any purpose other than for personal use. Therefore, reproduction, modification, storage in a retrieval system or retransmission, in any form or by any means, electronic, mechanical or otherwise, for reasons other than personal use, is strictly prohibited without prior written permission.
    https://www.whatsinproducts.com/contents/view/1/6
    Consumer Products Category Classification
    https://www.whatsinproducts.com/
  19. Cosmetic Ingredient Review (CIR)
  20. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    CHLORHEXIDINE
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  21. DailyMed
  22. Drugs and Lactation Database (LactMed)
  23. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  24. WHO Model Lists of Essential Medicines
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) license.
    https://www.who.int/about/policies/publishing/copyright
  25. EU Clinical Trials Register
  26. Hazardous Chemical Information System (HCIS), Safe Work Australia
  27. NITE-CMC
    Chlorhexidine - FY2009 (New/original classication)
    https://www.chem-info.nite.go.jp/chem/english/ghs/09-mhlw-0117e.html
  28. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  29. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Drugs listed in the Japanese Pharmacopoeia
    http://www.genome.jp/kegg-bin/get_htext?br08311.keg
    Risk category of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08312.keg
    Classification of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08313.keg
  30. Metabolomics Workbench
  31. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  32. NIPH Clinical Trials Search of Japan
  33. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  34. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  35. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  36. Wikidata
  37. Wikipedia
  38. PubChem
  39. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
    Anti-Infective Agents, Local
    https://www.ncbi.nlm.nih.gov/mesh/68000891
  40. GHS Classification (UNECE)
CONTENTS