Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.305 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEC
Value:
258.303 mg/m³
AF for intraspecies differences:
5
Justification:
worker default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.442 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL
Value:
146.5 mg/kg bw/day
AF for intraspecies differences:
5
Justification:
worker default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - workers

Toxicokinetics :

There are reports which suggest that professional soccer players were treated with 500mg of Clioquinol for an unspecified period. The individuals receiving Clioquinol had reduced incidence of diarrhea and no adverse effects were reported. Studies of 750 mg and 1000 mg of Clioquinol were also reported to have efficacy in the prevention of diarrhea and no adverse events were noted.Thus, it can be concluded that sinceClioquinolis likely to have low bio-accumulation potential in humans, no toxic effects were exhibited upon oral administration of the chemical for longer durations.

Acute toxicity :

Acute toxicity of Clioquinol to mouse by the oral route indicates that the substance exhibits acute toxicity by the oral route.But the acute values of inhalation does not exhibits acute toxicity by the inhalative route. Thus, it can be inferred that the target substance is non toxic to inhalation route of exposure but will qualify for oral toxicity.

 

Irritation / corrosion

In vivo studies of the substance show that the substance is irritating to skin and eyes, and so the substance is classified in any of the category as per the C&L regulation.

 

Sensitisation

Clioquinol was found to be sensitising to human skin bypatch test test..Ten patients with positive patch test reactions to clioquinol were retested in 1979 after an average interval of 6 years. On subsequent testing we also examined test reactions to other quinoline derivatives (including antimalarial drugs) and potassium iodide. All patients showed a positive reaction to clioquinol at retesting.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.062 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEC
Value:
127.391 mg/m³
AF for intraspecies differences:
10
Justification:
General population default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.221 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
146.5 mg/kg bw/day
AF for intraspecies differences:
10
Justification:
General population default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.61 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
73.25 mg/kg bw/day
AF for intraspecies differences:
10
Justification:
General population default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - General Population

DNEL derivation

Clioquinol is acute toxic to oral route in category 3, whereas by dermal and inhalation route it become non toxic ,shows irritation effect to skin and eye, is not genotoxic and is not developmental and reproductive toxic. 

In the absence of local effects following short-term or long-term exposure, no dose-response data are available and a quantitative dose descriptor is not derived. DNEL values for local exposure are therefore not calculated.

 

In the absence of acute systemic toxicity, no dose-response data are available and a quantitative dose descriptor is not derived. DNEL values for acute systemic effects are therefore not calculated.

 

A standard approach to deriving DNEL values would be to use the reproductive toxicity dataset and apply assessment factors as described in ECHA guidance documents. The critical endpoint is considered to be the NOAEL of 293 mg/kg bw/d in oral category.