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EC number: 200-238-7 | CAS number: 55-56-1
- 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
Endpoint summary
Administrative data
Description of key information
For the oral route a subchronic study in rats (using chlorhexidine digluconate solution in water to achieve the following nominal dose levels (as chlorhexidine base) through administration in drinking water: 50, 100 and 200 mg/kg bw/day). Additionally chronic oral studies have been performed with rats (using 20% chlorhexidine digluconate solution in water to achieve the following nominal dose levels (as chlorhexidine base) through administration in drinking water: 0, 5, 25 and 50 mg/kg bw/day; additional group was dosed with chlorhexidine at 50 mg/kg bw/day and para-chloranilin at 0,125 mg/kg bw/day) and dogs (using 20% chlorhexidine digluconate solution in water to achieve the following nominal dose levels (as chlorhexidine base) through administration in capsules: 0, 0.5, 5 and 40/25 mg/kg bw/d; highest dose was reduced after 28 w).
For dermal exposure data from a 13-week study with chlorhexidine diacetate in rabbits as well as from a 13-week bathing study in neonatal rhesus monkeys are taken into consideration. The dose levels expressed as chlorhexidine base administered in this 13-week dermal toxicity study in rabbits were: 0, 250, 500 or 1000 mg/kg bw/d, whereas in the 13-week bathing study in neonatal Rhesus monkeys an 8% (w/v as Chlorhexidine digluconate) was adminstered.
Due to the physico-chemical properties of the substance exposure via inhalation is unlikely. Therefore, testing for inhalation toxicity is scientifically not justified.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Dose descriptor:
- LOAEL
- 5 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Dose descriptor:
- NOAEL
- 250 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rabbit
Additional information
The results of toxicity studies with repeated administration of chlorhexidine digluconate in animals are summarised in the following Table.
Oral
A subchronic study has been conducted in rats and chronic studies have been conducted with rats and dogs.
Repeated dose toxicity of chlorhexidine digluconate (nominal dose levels in table expressed as chlorhexidine base)
Route |
Duration of study |
Species |
Nominal Dose levels (mg/kg · d) |
Results |
LO(A)EL mg/kg · d* |
NO(A)EL mg/kg · d* |
Feeding (capsules) |
1 year |
Dog |
0.5 |
Hepatic centrilobular fibrosis |
5 |
0.5 |
Drinking water |
2 years |
Rat |
5 Continuously |
Reactive histiocytosis of mesenteric lymph nodes, reversible |
5 |
not derived |
Drinking water |
3 months |
Rat |
50 |
Presence of giant cells in abdominal lymph nodes |
48.5 |
not derived |
A: pCA: para-chloroaniline
*Expressed as dose of chlorhexidine base.
In a chronic toxicity study comparable to OECD guideline 452 with rats, the only consistent treatment-related finding in rats was a histiocytosis of the mesenteric lymph nodes. There were no other histological effects on any organ or effects on haematology, clinical chemistry or urine analysis. The histiocytosis was reversible after cessation of exposure. There was no evidence of related damage to the intestinal mucosa or the submucosa which could be related to the histiocytosis in the mesenteric lymph node. The histiocytosis in treated rats is considered to be a reactive change and a local reaction which is restricted to and results from the presence of foreign bodies in the node.
Similar observations were described in an older subchronic study with rats. The only treatment-related change besides a reduced weight gain at the highest dose was the presence of giant cells in abdominal lymph nodes.
In contrast, dogs developed hepatic lesions after one year oral administration of chlorhexidine digluconate in capsules. At terminal sacrifice, there was an increase in macroscopic observations for the liver with white capsular striations and/or dark areas. Histopathology revealed treatment-related hepatic changes after 6 and after 12 months and after the 2-month recovery period. At the highest dose, changes were characterised by focal degeneration, necrosis and loss of hepatocytes and, in a few dogs, extensive irregular areas of necrosis and loss of hepatocytes over several liver lobules. Changes associated with these findings were focal mononuclear infiltrations, haemorrhages, bile duct hyperplasia, fibrosis, haemosiderosis, and acute inflammatory cell infiltrates. In animals of the mid dose group, treatment-related changes were characterised by centrilobular fibrosis. No such effects were observed at the lowest dose.
Dermal
Data are available from a non-guideline but well-conducted and described scientific study with neonatal Rhesus monkeys. The animals were washed daily for a three month period with 5 ml of an antimicrobial skin cleanser containing 8 %chlorhexidine digluconate, corresponding to a dermal daily applied dose of approx. 225 mg chlorhexidine base/500-600 cm² skin area (0.67 -0.8 mg/cm²). This value represents an upper bound estimate since the animals were washed with water afterwards. Although chlorhexidine is strongly bound to the skin, this is likely to have washed off some chlorhexidine digluconate.There were no treatment-related changes in haematology and serum chemistry and in organ histology compared to controls washed with water or cleanser free of chlorhexidine digluconate. Chlorhexidine was bound to the skin and, in some animals, very low concentrations could be detected in blood and organs, and also in faeces, but not in bile. It is likely that the presence of chlorhexidine in the body may have at least partially arisen through oral uptake from grooming.
A 13-week dermal toxicity study was performed with chlorhexidine diacetate in rabbits. Animals were exposed to the moistened test substance under occlusive conditions. The treatment caused minimal dermal irritation with erythema, oedema, desquamation and fissuring. In females, the activity of the aspartate aminotransferase and of the alanine aminotransferase were increased at >= 500 mg/kg/d. The incidences of hepatocellular degeneration/necrosis were 0, 1 (not significantly different from control), 5, and 7 with increasing dose. In male the incidence was not statistically significant different from the control. The liver necrosis was graded as “minimal” in all animals. 250 mg/kg/d was considered as a NOEL for systemic effects.
Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: lymph nodes
Repeated dose toxicity: dermal - systemic effects (target organ) digestive: liver
Justification for classification or non-classification
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