Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 242-354-0 | CAS number: 18472-51-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Carcinogenicity
Administrative data
Description of key information
Carcinogenicity studies were performed with oral administration of chlorhexidine to rats and mice. In both studies there was no evidence for a carcinogenic activity.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1978-03-02 to 1980-05-06
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Deviations:
- not applicable
- GLP compliance:
- yes
- Remarks:
- Auditing in accordance with ICI’s policies and procedures for GLP
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: ICI, Alderley Park Breeding Unit, UK
- Age at study initiation: 3-5 weeks
- Weight at study initiation: 46-128 g (m); 41-120 g (f)
- Housing: RCl cages, 5 of one sex in each cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 50 +/- 15
- Air changes (per hr): >15
- Photoperiod (hrs dark / hrs light): 12 / 12 - Route of administration:
- oral: feed
- Details on exposure:
- Rate of preparation of diet (frequency): Dietary concentrations were adjusted weekly until week 58 and then fortnightly.
Vehicle: Chlorhexidine digluconate was added to the diet as a 20 % aqueous solution (equivalent to 11.26 % chlorhexidine base).
The concentration of chlorhexidine in the diet was adjusted weekly and routinely monitored throughout the study and was between 95 % and 105 % of the theoretical value except for a few values.
Three similarly constituted groups of rats received unmedicated diet and served to generate contemporaneous control data. Additional groups of 50 male and 50 female rats also received the test substance at the appropriate dosage, or unmedicated diet and were assigned to interim sacrifice after 4, 13, 26, 39 52, 65, 78, 91 weeks of treatment. With the exception of weeks 4 and 13 when 10 rats per sex from each group were sacrificed, 5 rats per sex per group were sacrificed after each elapsed time period. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Homogeneity: by blending in a srew type mixer
- Duration of treatment / exposure:
- 105 weeks
- Frequency of treatment:
- continuously via diet
- Post exposure period:
- none
- Remarks:
- Doses / Concentrations:
0, 5, 25 or 50 mg/kg bw/d (as chlorhexidine base); ca. 0, 8.9, 44.5 or 89 mg/kg bw/d (as chlorhexidine digluconate)
Basis:
nominal in diet - No. of animals per sex per dose:
- 50 m / 50 f
- Control animals:
- yes
- Details on study design:
- Interim sacrifice(s): after 4, 13, 26, 39, 52, 65, 78 and 91 weeks
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS:
-Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS:
-Time schedule: once weekly
BODY WEIGHT:
-Time schedule for examinations: on day 0 and weekly thereafter
FOOD CONSUMPTION AND COMPOUND INTAKE:
-Weight of food consumed by each cage of mice was calculated weekly (food offered / food remaining)
FOOD EFFICIENCY:
-Group mean food conversion ratios were calculated at weekly intervals for the first 13 weeks and at quarterly intervals thereafter
WATER CONSUMPTION:
-Time schedule for examinations: once daily
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No - Sacrifice and pathology:
- Final sacrifice: after 105 weeks
Histopathology: At termination of study from all dose groups with all major organs - Other examinations:
- The concentration of chlorhexidine and of p-chloroaniline in the blood and organs were assessed at all interim sacrifice time points and at the end of the study.
- Statistics:
- yes
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- Body weight/Weigth gain:
50 mg/kg bw/d (males) and >= 25 mg/kg bw/d (females): decreased compared with respective control from week 39 of treatment
Macroscopic investigations:
About 30 % of all animals had lesions of the hard palate after 45-46 weeks. The appearance of this lesion was not related to the administration of chlorhexidine digluconate but to the presence of the fibres in the non-pelleted diet. The incidence of animals bearing palpable tumours and the total numbers of palpable swellings were not increased by treatment with chlorhexidine digluconate.
Histopathology:
No increased incidences of benign and malignant neoplasms of individual tumour types. In rats from all groups, periodontal ulcers and sinuses with inflammation were seen. These were caused by long, sharp vegetable fibres in the diet that was fed to the animals during the initial 45 weeks. Squamous cell carcinomas, mostly on the base of chronically inflamed ulcers and sinuses, developed in a total number of 74 animals from all groups. There was, however, no relationship between the development of the described hard palate lesions or these tumours and the presence of chlorhexidine digluconate in the diet. The only observation related to administration of chlorhexidine digluconate was the increase in the percentage number of animals showing the presence of pigment-laden macrophages in the mesenteric lymph nodes (severity grade II).
Other examinations:
The concentration of chlorhexidine in blood, brain, lung, liver, kidney and mesenteric lymph nodes increased with dose of chlorhexidine digluconate indicating that at least some of the test substance was absorbed from diet. The concentration of chlorhexidine in the brain was consistently lower than that in the blood, while the concentrations in blood, liver and lung were comparable. The highest concentration was found in the kidneys and in the mesenteric lymph nodes after 21 months of feeding chlorhexidine digluconate. The concentrations of p-chloroaniline in the mentioned organs and in blood were very low throughout the study and at the limit of detection at many time points.
Time to tumours:
The times of appearance of palpable swellings was not different between groups of animals treated with chlorhexidine digluconate and controls. - Dose descriptor:
- LOEL
- Effect level:
- 5 other: mg/kg bw/day (as chlorhexidine base)
- Sex:
- male/female
- Basis for effect level:
- other: pigment-laden macrophages in mesenteric lymph nodes (grade II)
- Conclusions:
- Under the conditions of the present study, there was no evidence for a carcinogenic effect of chlorhexidine digluconate in rats following oral administration of doses up to the MTD.
- Executive summary:
Carcinogenicity study with dietary administration of test compound to rats for at least 105 weeks.
Body weight and body weight gain in male rats at 50 mg/kg bw/d and in female rats at >= 25 mg/kg bw/d were slightly lower than that of the corresponding control groups indicating that the maximum tolerated dose (MTD) was reached.
Kinetic data show that at least some of the chlorhexidine is absorbed from the diet. The concentration of chlorhexidine found in blood and various organs of animals increased with dose and time. The highest concentrations were found in the kidneys and in the mesenteric lymph nodes.
There was no evidence of a chlorhexidine-related increase in the incidence of any benign or malignant tumour. Neither the distribution among the groups nor the predominant macropathological entities identified at necropsy showed any effects that could be related to the treatment of the animals with chlorhexidine digluconate. The only histological effect that is attributed to the treatment with chlorhexidine digluconate is an increase in the percentage number of animals showing the presence of pigment-laden macrophages in the mesenteric lymph nodes.
LOEL (based on pigment-laden macrophages in mesenteric lymph nodes, grade II): 5 mg chlorhexidine mg/kg bw/d (equal to 8.9 mg chlorhexidine digluconate/kg bw/d).
The treatment gave no evidence for a carcinogenic effect of chlorhexidine digluconate.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LOAEL
- 8.9 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
Justification for classification or non-classification
Carcinogenicity studies were performed with oral administration of chlorhexidine to rats and mice. In both studies there was no evidence for a carcinogenic activity.
Therefore, there is no need for a classification.
Additional information
The results of carcinogenicity studies in animals are summarised in the following Table:
Route |
Species |
dose levels |
Tumours |
Oral, food |
Mouse |
0, 100, 200, 400 mg chlorhexidine/kg bw d = 0, 175, 350, 700 or 1400 mg chlorhexidine digluconate/kg bw d; daily |
The incidence and distribution of benign and malignant tumours showed no substance-related changes |
Oral, food |
Rat |
0, 5, 25, 50 mg chlorhexidine/kg bw d = 0, 8.8, 44 or 88 mg Chlorhexidine digluconate/kg bw d; daily |
The incidence and distribution of benign and malignant tumours showed no substance-related changes |
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.