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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 204-984-4 | CAS number: 130-26-7
- 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
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Qualifier:
- according to guideline
- Guideline:
- other:
- Principles of method if other than guideline:
- Clioquinol Toxcity in Dogs
- GLP compliance:
- not specified
- Species:
- dog
- Strain:
- Beagle
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Housing:housed singly
- Diet (e.g. ad libitum):dry diet (Spratt’s Dog Diet P62, Spillers Ltd., Barking, Essex)
- Water (e.g. ad libitum):Water was freely available
- Acclimation period: - Route of administration:
- oral: unspecified
- Vehicle:
- other: gelatine capsules
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 25 Weeks
- Frequency of treatment:
- Intermittent
- Remarks:
- Doses / Concentrations:
0,250 ,400 mg of pure clioquinol/kg of body weight/day.
Basis: - No. of animals per sex per dose:
- Control:6 dogs
250 mg/kg bw/day:6 dogs
400 mg/kg bw/day:6 dogs - Control animals:
- yes, concurrent vehicle
- Details on study design:
- Nine male and 9 female Beagles were allotted to 3 groups: group 1 received empty gelatine capsules and acted as control; group 2 was given 250 mg; and
group 3 400 mg of pure clioquinol/kg of body weight/day. The test compound was administered undiluted in gelatine capsules, daily for 25 weeks.
The dogs were housed singly and were initially offered 400 g of a dry diet each morning; 200 ml cows’ milk was offered, on week-days only, throughout the experiment.Water was freely available. - Observations and examinations performed and frequency:
- Ophthalmoscopic examination revealed paleness of the optic papilla in one female dog receiving the high dosage. The pupillary light reflex was
found to be sluggish.
Haematological monitoring showed that the red cell counts tended to be lower in the dosed groups than in the controls. This was noted after 4 weeks
of administration of the test compound and persisted till the end of the study. The only other abnormality detected as a result of laboratory investigations that could have been attributable to treatment was a higher mean urinary creatine: creatinine ratio in the dosed groups than in control animals,
indicative of a disturbed muscle function. This was found after 12, 18, 20 and 22 weeks’ administration of the test compound, but after 24 weeks the
means were similar in all groups.
Macroscopic post-mortem examination revealed atrophy of the limb musculature in 3 females in group 3 that had survived the entire 25-week
treatment period; this muscle wasting was associated with general debility and attributed to treatment with the test compound.The absolute organ weights were considered to be within normal limits. However, in the dogs of groups 2 and 3, the mean liver weight expressed as a percentage of the body weight was significantly greater than the control values (P < 0.05), a not infrequent finding in toxicity studies .
Urineanalysis:urine samples were obtained for complete urine analysis, including examination of sediment
Histological changes were identified in the dorsal columns of the spinal cord in one dog receiving 250 mg/kg daily and in 4 dogs receiving 400mg/kg daily. In one of the dogs given the high dose the changes were present at various levels of the cord, whereas in the dog receiving 250 mg/kg daily
they were restricted to the cervical and thoracic regions, and in the 3 remaining high dose-level animals (two of which were the dogs killed on day 11
the cervical region only was affected. In these last-mentioned animals, the changes were minimal and located close to the nucleus gracilis of the medulla.
The lesions were of a dystrophic nature, probably acute in onset and werenot considered to be due to any ageing process. The morphological features included axonal swelling and degeneration, myelin breakdown with myelinophagia and occasional astrocyte activation (Figs. l-4). Similar changes,
including sxonal swelling, were seen in the optic nerve of one dog . Although the peripheral nerves and the spinal and autonomic ganglia
were examined thoroughly, no pathological changes were detected. Nor were any pathological changes detected in sections taken from the flexor muscleof the 5th digit and stained with Sudan black B . The myelin sheaths were preserved and the muscular motor and anulospiral endings were demonstrated. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table)
The animals were killed and the organs examined macroscopically. The major organs were weighed, and pieces of these and other tissues were removed and prepared for histological examination.
HISTOPATHOLOGY: Yes (see table) / No / No data - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- abnormal gait with partial or complete hind limb paralysis, yellowing of the hair and patchy hair loss.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- abnormal gait with partial or complete hind limb paralysis, yellowing of the hair and patchy hair loss.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Individual animals on 250 mg/kg daily showed episodes of depressed body weight gain and/or weight loss, alternating with periods of normal development.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- loss of appetite from the first week of dosing.
- Ophthalmological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Ophthalmoscopic examination revealed paleness of the optic papilla in one female dog receiving the high dosage. The pupillary light reflex was found to be sluggish
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Haematological monitoring showed that the red cell counts tended to be lower in the dosed groups than in the controls
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- Neurological examination revealed disturbance of the placing and postural reactions in all the animals in group 3 and some in group 2.
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- The absolute organ weights were considered to be within normal limits.
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Macroscopic post-mortem examination revealed atrophy of the limb musculature in 3 females in group 3 that had survived the entire 25-week treatment period;
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Histological changes were identified in the dorsal columns of the spinal cord in one dog receiving 250 mg/kg daily and in 4 dogs receiving 400 mg/kg daily.
- Dose descriptor:
- LOEL
- Effect level:
- 250 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: depressed body weight gain and/or weight loss,disturbance of the placing and postural reactions
- Critical effects observed:
- not specified
- Conclusions:
- The repeated dose toxicity LOEL (Low observed effect level ) of clioquinol was observed at a dose concentration of 250 mg/kg bw (total dose) in a 25 weeks study period .
- Executive summary:
The study was conducted to test Clioquinol toxcity in dogs at a dose level of 0, 250, 400 mg of pure clioquinol/kg of body weight/day for 25 weeks. Individual animals on 250 mg/kg daily showed episodes of depressed body weight gain and/or weight loss, alternating with periods of normal development. Ophthalmoscopic examination revealed paleness of the optic papilla in one female dog receiving the high dosage. The pupillary light reflex was found to be sluggish.Histological changes were identified in the dorsal columns of the spinal cord in one dog receiving 250 mg/kg daily and in 4 dogs receiving 400 mg/kg daily. thus we can conclude that the repeated dose toxicity LOEL (Low observed effect level ) of clioquinol was observed at a dose concentration of 250 mg/kg bw (total dose) in a 25 weeks study period .
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LOAEL
- 250 mg/kg bw/day
- Study duration:
- chronic
- Species:
- dog
- Quality of whole database:
- The data is K2 level as the data has been obtained from an experimental study from the journal " Toxicology" .Based upon this available data it is expected that this chemical clioquinol does not exhibit repeated dose oral toxicity to dog.
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Justification for type of information:
- QSAR prediction: migrated from IUCLID 5.6
- Qualifier:
- according to guideline
- Guideline:
- other: Estimated data
- Principles of method if other than guideline:
- Prediction is done using QSAR Toolbox version 2.3.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- not specified
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- weekly 5
- Control animals:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- body weight decrease
- Dose descriptor:
- LOEL
- Effect level:
- 159.486 other: mg/kg/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: not specified
- Remarks on result:
- other: not specified
- Critical effects observed:
- not specified
- Organ:
- not specified
- Conclusions:
- The repeated dose toxicity LOEL (Lowest observed effect level) of clioquinol to rat by the inhalation route was estimated at a dose concentration of 159.4855 mg/kg bw/day.On the basis of this LOEL value it is concluded that the test substance is not toxic to rat by the inhalative route below the above mentioned dose.
- Executive summary:
The repeated dose toxicity LOEL (Lowest observed effect level) of clioquinol to rat by the inhalation route was estimated at a dose concentration of 159.4855 mg/kg bw/day.On the basis of this LOEL value it is concluded that the test substance is not toxic to rat by the inhalative route below the above mentioned dose.
Reference
The
prediction was based on dataset comprised from the following
descriptors: "effect LOEL"
Estimation method: Taking average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain
(("a"
or "b" or "c" or "d" or "e" or "f" )
and ("g"
and "h" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Phenols (Acute toxicity) by
US-EPA New Chemical Categories
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as Arene AND Aryl halide AND
Heterocyclic fragment AND Phenol AND Pyridine(substituted) by Organic
functional groups
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as Aryl AND Aryl halide AND Fused
heterocyclic aromatic AND Phenol AND Pyridine AND Quinoline/
Isoquinoline by Organic Functional groups (extended)
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as Aryl halide AND Heterocyclic
fragment AND Phenol AND Pyridine(substituted) by Organic functional
groups (nested)
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as Aryl halide AND Overlapping
groups AND Phenol AND Quinoline/ Isoquinoline by Organic Functional
groups (nested)(extended)
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Aromatic compound AND Aryl
chloride AND Aryl halide AND Aryl iodide AND Halogen derivative AND
Hydroxy compound AND Phenol by Organic functional groups, Norbert Haider
(checkmol)
Domain
logical expression index: "g"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 2.61
Domain
logical expression index: "h"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 3.64
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- 159.486
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- The data is K2 level as the data has been obtained from QSAR model considered by OECD.
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity (Oral)
For Repeated dose toxicity
Based on the various studies available with Klimish rating 2 for the target substances for CAS: 130-26-7.This data is combined with the prediction done using the QSAR toolbox for the target chemical based on similar category approach, the results is summarized as follows
Sr. No |
End point |
Value |
Species |
Route |
Effects |
Remarks |
1 |
LOEL |
536 mg/ kgbw/day |
Rat |
Oral |
Histopathological findings were observed |
Predicted data for target chemical |
2 |
LOEL |
250 mg/kg bw/d |
Dog |
Oral |
depressed body weight gain and/or weight loss,disturbance of the placing and postural reactions |
Publication data for target chemical |
2 |
LOEL |
200 mg/kg bw/d |
Dog |
Oral |
myocardial degeneration,gross pathology |
Publication data for target chemical |
Based on the studies summarized in the above table with oral routes it can be observed that LOEL values varies from 200 - 536 mg/Kg bw/ d. The effects observed on the these doses was listed as follows
· Histopathological findings were observed
· depressed body weight gain and/or weight loss,disturbance of the placing and postural reactions.
· myocardial degeneration,gross pathology
Thus based on above discussion it can be concluded that substance CAS: 130-26-7 is expected to show the stoxicological effect based on above effects.Since low effect dose value (LOAEL) is 200 mg/Kg bw/d which was also supported by the predicted LOEL value of 536 mg/kg bw/d, thus based on this value it can be concluded that substance CAS: 130-26-7 is considered to be not toxic to repeated dose via oral route for the above mentioned dose. Also there are no known evidence of adverse effect to Human of CAS: 130-26-7.
Repeated dose toxicity: inhalation
The repeated dose toxicity LOEL (Lowest observed effect level) of clioquinol to rat by the inhalation route was estimated at a dose concentration of 159.4855 mg/kg bw/day.On the basis of this LOEL value it is concluded that the test substance is not toxic to rat by the inhalative route below the above mentioned dose.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The repeated dose toxicity LOEL (Low observed effect level ) of clioquinol was observed at a dose concentration of 250 mg/kg bw (total dose) in a 25 weeks study period
Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
The repeated dose toxicity LOEL (Lowest observed effect level) of clioquinol to rat by the inhalation route was estimated at a dose concentration of 159.4855 mg/kg bw/day.On the basis of this LOEL value it is concluded that the test substance is not toxic to rat by the inhalative route below the above mentioned dose.
Justification for classification or non-classification
The substance clioquinol do not show repeated dose toxicity effect for oral and inhalation route and thus will not be considered for further classification.
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.