Clioquinol

Endpoint summary

Description of key information

The substance clioquinol was found to be irritaing in skin and eye category.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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:

other: Estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 2.3.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Score:

2.95

Reversibility:

no data

Remarks on result:

other: Mild irritation

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

((((((((("a" and ("b" and ( not "c") ) ) and ("d" and ( not "e") ) ) and ("f" and ( not "g") ) ) and "h" ) and ("i" and ( not "j") ) ) and ("k" and ( not "l") ) ) and "m" ) and ("n" and ( not "o") ) ) and ("p" and "q" ) )

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 No alert found by DNA binding by OASIS

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as MA: Nitrenium ion formation OR MA: Nitrosonium ion formation OR MA: Radical mechanism by ROS formation OR Mechanistic Domain: Radical OR Mechanistic Domain: SN1 OR Nitro compounds by DNA binding by OASIS

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alkyl phenols OR Allyl benzenes OR Arenes OR Hydroquinones OR MA: Carbenium Ion Formation OR MA: P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Mechanistic Domain: Michael addition OR Mechanistic Domain: SN1 by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as MA: Direct Acting Schiff Base Formers OR Mechanistic Domain: Schiff Base Formers OR Mono-carbonyls by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Phenols and Anilines by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Esters OR Phenols, Poly by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At AND Group 17 - Halogens I by Chemical elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 17 - Halogens Br by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis

Domain logical expression index: "n"

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: "o"

Referential boundary: The target chemical should be classified as Arene OR Cycloalkane OR Cycloalkene by Organic functional groups (nested)

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.42

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.97

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

By primary dermal irritation index (PDII) from QSAR, skin irritation score of clioquinol estimated as 2.95.Based upon this score it is indicated that clioquinol is mildly irritating to the skin of rabbit which is not adequate for classification as a skin irritant. Therefore, it can be concluded that clioquinol is irritating to the skin of rabbit.

Executive summary:

By primary dermal irritation index (PDII) from QSAR, skin irritation score of clioquinol estimated as 2.95.Based upon this score it is indicated that clioquinol is mildly irritating to the skin of rabbit which is not adequate for classification as a skin irritant. Therefore, it can be concluded that clioquinol is irritating to the skin of rabbit.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

human

Strain:

not specified

Duration of treatment / exposure:

no data

Observation period (in vivo):

no data

Irritation parameter:

overall irritation score

Basis:

mean

Remarks on result:

other: irritant

Other effects:

An investigating committee reported in 1974 knowledge of more than a dozen children with optic neuropathy from clioquinol. Less than half had
symptoms of peripheral neuropathy

Some of the earliest suspicions of toxicity affecting vision were in relation to children who were being treated for acrodermatitis enteropathica for long periods with large doses when their vision was found to be much impaired, and optic atrophy was diagnosed.

Some children had difficulty in walking as well as poor vision. An investigating committee reported in 1974 knowledge of more than a dozen children with optic neuropathy from clioquinol. Less than half had symptoms of peripheral neuropathy.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The clioquinol irritating to the human eyes .it is found that more than a dozen children with optic neuropathy from clioquinol

Executive summary:

The clioquinol irritating to the human eyes .it is found that more than a dozen children with optic neuropathy from clioquinol

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

By primary dermal irritation index (PDII) from QSAR, skin irritation score of clioquinol estimated as 2.95.Based upon this score it is indicated that clioquinol is mildly irritating to the skin of rabbit . also the supportong study indicates that clioquinol cause mild irritation to skin. Therefore, it can be concluded that clioquinol is mild irritating to the skin of rabbit & human..

Eye irritation

The clioquinol was found to be irritating to human eye ,it can cause optic neuropathy in human.An investigating committee reported shows that more than a dozen children with optic neuropathy from clioquinol. Less than half subjects had symptoms of peripheral neuropathy.thus from above discussion we can conclude that the test substance cause eye irritation.

Justification for selection of skin irritation / corrosion endpoint:

By primary dermal irritation index (PDII) from QSAR, skin irritation score of clioquinol estimated as 2.95.Based upon this score it is indicated that clioquinol is mildly irritating to the skin of rabbit . also the supporting study indicates that the test substance can cause irritation to human skin.Therefore, it can be concluded that clioquinol is irritating to the skin of rabbit & human.

Justification for selection of eye irritation endpoint:

The clioquinol was found to be irritating to human  eye ,it can cause optic neuropathy in human.

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: moderately irritating

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