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Description of key information

Acute oral toxicity: 

The acute oral toxicity dose (LD50) was considered based on different studies conducted on mice and guinea pigs for the test chemical. The LD50 value is 69 mg/kg bw. The study concluded that LD50 is between 50-300 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “category 3” for acute oral toxicity.

Acute Inhalation Toxicity:

The acute inhalation toxicity dose (LC50) was considered based on different studies conducted on rats and mice for the test chemical. The LC50 value is 407.2346 mg/L (407234.6 mg/m3). The study concluded that LC50 is >5 mg/L, for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute inhalation toxicity.

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) was considered based on different studies conducted on rats for the test chemical. The studies concluded that LD50 value is >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute 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:
Standard acute method
GLP compliance:
not specified
Test type:
standard acute method
Species:
mouse
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
69 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Details of toxic effects not reported other than lethal dose value
Mortality:
Lethal dose, 50 percent kill
Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of clioquinol in rodent - mouse was found to be 69 mg/kg of body weight. Acute toxicity of clioquinol to rodent - mouse by oral route indicates that clioquinol exhibits acute toxicity by the oral route in category 3.


Executive summary:

The acute oral median lethal dose (LD50) of clioquinol in rodent - mouse was found to be 69 mg/kg of body weight. Acute toxicity of clioquinol to rodent - mouse by oral route indicates that clioquinol exhibits acute toxicity by the oral route in category 3.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
69 mg/kg bw
Quality of whole database:
The data is K2 level as the data has been obtained from an experimental study from the reliable handbook source SAX which is considered to be an authoritative source of information.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
other: Acute Rodent Inhalation Toxicity Test
Species:
mouse
Strain:
Swiss Webster
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
not specified
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LC50
Effect level:
407.235 other: mg/L
Based on:
test mat.
Exp. duration:
4 h





The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Taking average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

("a" and ("b" and "c" ) )

Domain logical expression index: "a"

Similarity boundary:Target: c1(I)c(O)c2c(c(Cl)c1)cccn2
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.61

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.45

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The 4 hrs acute inhalation median lethal concentration (LC50) of clioquinol in mouse was found to be 407.2346 mg/L.Acute toxicity of clioquinol to mouse by the inhalation route indicates that clioquinol does not exhibits acute toxicity by the inhalative route within the doses mentioned.
Executive summary:

The 4 hrs acute inhalation median lethal concentration (LC50) of clioquinol in mouse was found to be 407.2346 mg/L.Acute toxicity of clioquinol to mouse by the inhalation route indicates that clioquinol does not exhibits acute toxicity by the inhalative route within the doses mentioned.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
407.235
Quality of whole database:
The data is K2 level as the data has been obtained from QSAR model considered by OECD.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
experimental data from various test chemicals
Justification for type of information:
Data is summarized based on the available information from various test chemicals.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
WoE report is based on 2 acute dermal toxicity studies as- WoE 2 and WoE 3.
Acute dermal toxicity test was carried out to study the effects of the test chemicals on rodents.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
other: 1. Wistar 2. not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
1. TEST ANIMALS
- Source: Institute for Industrial Research and Toxicology Ghaziabad,
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 200±20g
- Fasting period before study: Animals were fasted overnight prior to test and food was offered three hours after dosing.
- Housing:Groups of three animals of same sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle, and bedding of clean paddy husk.
- Identification :By cage tag and corresponding colour body marking
- Diet (e.g. ad libitum): Pelleted feed,
- Water (e.g. ad libitum):Fresh and clean water filtered through ‘Aqua Guard on line water filter’, was kept in glass bottles Ad libitum
- Acclimation period: The healthy wistar albino rats selected for study acclimatized to standard laboratory condition for period of one week under close Veterinary supervision.
- Randomization:After acclimation and Veterinary examination all the animals randomly divided into two groups and each group having five male and five female rats.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature between 22-25°C
- Humidity (%): 40-60%
- Air changes (per hr): Air conditioned rooms with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
2. not specified
Type of coverage:
other: 1. occlusive 2. Dermal
Vehicle:
other: 1. water 2. not specified
Details on dermal exposure:
1. TEST SITE
- Area of exposure: back skin of total body surface area
- % coverage: Approximate 10 percent
- Type of wrap if used: The test compound was held in contact with the skin with an impervious dressing secured in place with an adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dressing was removed and the site of application was cleaned with lukewarm water wiping the test compound.
- Time after start of exposure: 24 hours

VEHICLE
- Concentration (if solution): The test compound was moistened with distilled water and then applied at the dose level of 2000 mg/kg b.wt.
2. not specified
Duration of exposure:
1. 24 hours
2. not specified
Doses:
1. 2000 mg/kg b.wt.
2. 2000 mg/kg bw
No. of animals per sex per dose:
1. No. of animals per dose group : 10 (5male & 5 female)
2. not specified
Control animals:
not specified
Details on study design:
1. - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All the animals were observed for mortality at 30 minutes time interval for first six hours on the day of test compound administration and thereafter twice a day for 14 days. The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment). The treated animals were closely observed for clinical signs of intoxication, first 4 hours and thereafter for every 1 hrs interval for 24 hrs after dosing and twice a day for 14 days. All the rats were observed at least twice daily with the purpose of recording any symptoms of ill-health or behavioral changes. These observations included changes in skin and fur in the eyes and mucous membranes, respiratory, circulatory, central nervous, and autonomic nervous systems, somatomotor activity and behavioral changes. The following clinical signs were observed in female rats to characterize with erythema, hypersensitivity, edema etc.
- Necropsy of survivors performed: yes, necropsy was carried out on all the animals that died during the study or surviving animals were sacrificed at the end of the study to observe any gross pathological changes.
2. not specified
Statistics:
not specified
Preliminary study:
1. LIMIT TEST (2000 mg/kg b.wt): Ten healthy wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test compound Diiodohydroxyquinoline was applied dermally at the dose level of 2000 mg/kg b.wt for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all the animals at the termination of the study.
2. not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed
Mortality:
1. The test compound when applied dermally at the dose level of 2000 mg/kg b.wt. on Wistar albino rats did not produce any mortality during the observation period of 14 days
2. No mortality was observed at 2000 mg/kg bw
Clinical signs:
The test compound did not produce any clinical signs when applied dermally at the dose level of 2000mg/kg b.wt. during the observation period of 14 days
Body weight:
The body weight of each animal was recorded on day 7th and 14th (post treatment) showed normal gain as compared to control group
Gross pathology:
1. NECROPSY FINDING
EXTERNAL
i.Skin- Skin and hair coat was observed wet.
ii.All external orifices- Normal
B. INTERNAL
i. Subcutaneous- No changes were observed.
ii. Superficial and deep lymph nodes- No change in mesenteric lymph node.
ABDOMINAL CAVITY
i.Opening and general examination- In the abdominal cavity all the organs were present in normal position.
ii.Spleen- No changes were recorded.
iii.Digestive system- No gross changes were observed in stomach and intestine.
iv.Liver and biliary ducts- No gross pathological changes were observed
v.Excretory system- No gross pathological changes were observed.
vi.Adrenal- Observed normal.
vii.Male/female genital organs – Showed normal colour, consistency and no inflammatory changes.
2. THORACIC CAVITY
i.Opening and general examination- Thoracic cavity was found to be normal without any fluid, mucous or blood etc.
ii.Lungs- No changes were recorded.
iii.Heart- No changes were observed in color and consistency. Heart found normal.
iv.Thyroid- Normal in shape, size and surface.
3. CRANIAL CAVITY
Brain- Normal in shape and size.
2. not specified
Other findings:
not specified
Interpretation of results:
other: Not classified
Conclusions:
According to CLP regulation, the test chemical cannot be classified for acute dermal toxicity, as the LD50 value is >2000 mg/kg bw.
Executive summary:

In different studies, the given test chemical has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for test chemical. The studies are summarized as below –

1. The acute dermal toxicity study of the given test chemical was conducted on Wistar albino rats. This study was conducted according to OECD guideline 402 for testing of chemicals. The summary of the study given as follows - In limit test (2000 mg/kg b.wt) - 10 healthy wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test compound was applied dermally at the dose level of 2000 mg/kg b.wt for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all the animals at the termination of the study. The test chemical applied at the dose level of 2000 mg/kg b.wt in Wistar albino rats did not produce any mortality as well as clinical signs during observation period of 14 days. Necropsy findings did not reveal any significant gross pathological changes. After 72 hrs. a confirmatory test was conducted in same species of animals to confirm the limit test of test compound (OECD-402 guidelines). 10 healthy Wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test chemical was applied dermally at the dose level of 2000 mg/kg b.wt for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals which were died during the study or were sacrificed at termination of the study. No mortality was recorded in Wistar albino rats after administration of test chemical at the dose level of 2000 mg/kg b.wt. throughout the observation period. The test chemical applied at the dose level of 2000 mg/kg b.wt. did not produce any clinical signs of intoxication as well as dermal irritation in Wistar albino rats. The body weight of each animal recorded on day 0, 7th and 14th showed normal increase and there was no significant increase or decrease in weight was recorded. Therefore, result obtained from present investigation can be conclude that the acute dermal LD50 of the test chemical in Wistar albino rats when applied by dermal route was considered to be >2000 mg/kg b.wt. From this it is concluded that the test chemical is non toxic by dermal route in an acute study of 14 days

2. Acute dermal toxicity study of the given test chemical was conducted in rats at the concentration of 2000 mg/kg bw. No mortality was observed at 2000 mg/kg bw. Therefore, LD50 value was considered to be >2000 mg/kg bw, when rats were treated with the test chemical by dermal application.

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from study report.

Additional information

Acute oral toxicity:

In different studies, the given test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in mice and guinea pigs for test chemical. The studies are summarized as below –

1. The acute oral median lethal dose (LD50) of test chemical in rodent - mouse was considered to be 69 mg/kg of body weight. Acute toxicity of test chemical to rodent - mouse by oral route indicates that it exhibits acute toxicity by the oral route in category 3.

2. The acute oral LD50 of test chemical in guinea pig was considered to be 175 mg/kg of body weight. Acute toxicity of test chemical to guinea pig by oral route indicates that it exhibits acute toxicity by the oral route in category 3.

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is between 50-300 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “category 3” for acute oral toxicity.

Acute inhalation toxicity:

In different studies, the given test chemical has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for test chemical. The studies are summarized as below –

1. The 4 hrs acute inhalation median lethal concentration (LC50) of test chemical in mouse was considered to be 407.2346 mg/L. Acute toxicity of test chemical to mouse by the inhalation route indicates that it does not exhibits acute toxicity by the inhalative route within the doses mentioned.

2. The 4 hrs acute inhalation median lethal concentration (LC50) of test chemical in rat was considered to be 151.9451 mg/L. Acute toxicity of test chemical to rat by the inhalation route indicates that it does not exhibits acute toxicity by the inhalative route within the doses mentioned.

Thus, based on the above summarised studies on test chemical, it can be concluded that LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute inhalation toxicity.

Acute Dermal Toxicity:

In different studies, the given test chemical has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for test chemical. The studies are summarized as below –

1. The acute dermal toxicity study of the given test chemical was conducted on Wistar albino rats. This study was conducted according to OECD guideline 402 for testing of chemicals. The summary of the study given as follows - In limit test (2000 mg/kg b.wt) - 10 healthy wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test compound was applied dermally at the dose level of 2000 mg/kg b.wt for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all the animals at the termination of the study. The test chemical applied at the dose level of 2000 mg/kg b.wt in Wistar albino rats did not produce any mortality as well as clinical signs during observation period of 14 days. Necropsy findings did not reveal any significant gross pathological changes. After 72 hrs. a confirmatory test was conducted in same species of animals to confirm the limit test of test compound (OECD-402 guidelines). 10 healthy Wistar albino rats of both sex (ranging b.wt 200±20 gm) selected for study after acclimatization. Approximate 10 percent back skin of total body surface area was prepared 24 hrs prior to application of test compound. The test chemical was applied dermally at the dose level of 2000 mg/kg b.wt for each animal. The treated animals were observed for clinical signs of intoxication and mortality at different time interval for a period of 14 days. The body weight of each rat was observed on day 0 (pre treatment), 7th and 14th (post treatment). The necropsy was performed on all animals which were died during the study or were sacrificed at termination of the study. No mortality was recorded in Wistar albino rats after administration of test chemical at the dose level of 2000 mg/kg b.wt. throughout the observation period. The test chemical applied at the dose level of 2000 mg/kg b.wt. did not produce any clinical signs of intoxication as well as dermal irritation in Wistar albino rats. The body weight of each animal recorded on day 0, 7th and 14th showed normal increase and there was no significant increase or decrease in weight was recorded. Therefore, result obtained from present investigation can be conclude that the acute dermal LD50 of the test chemical in Wistar albino rats when applied by dermal route was considered to be >2000 mg/kg b.wt. From this it is concluded that the test chemical is non toxic by dermal route in an acute study of 14 days.

2. Acute dermal toxicity study of the given test chemical was conducted in rats at the concentration of 2000 mg/kg bw. No mortality was observed at 2000 mg/kg bw. Therefore, LD50 value was considered to be >2000 mg/kg bw, when rats were treated with the test chemical by dermal application.

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, the given test chemical cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies on test chemical, it can be concluded that LD50 value is between 50-300 mg/kg bw, for acute oral toxicity; LD50 value is >2000 mg/kg bw, for acute dermal toxicity; and LC50 value is >5 mg/L, for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, the given test chemical can be classified in “category 3” for acute oral toxicity and cannot be classified for acute dermal and acute inhalation toxicity.