Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.35 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
4.41 mg/m³
Explanation for the modification of the dose descriptor starting point:

No reliable repeated dose toxicity study with imazalil sulphate is available. Data generated with the related substance imazalil is used to select a dose descriptor starting point. The NOAEL of 5 mg/kg/day established in the 6 -month chronic oral repeated dose toxicity study in rats (oral route, EU Method B33; Til, 1983) was used to derive a DNEL long-term, systemic effects via the inhalation route. After route-to-route extrapolation from oral to inhalation, the dose descriptor starting point NOAEC is 4.41 mg/m³ =5 mg/kg/day x 1/0.38 m³/kg/day x 0.67 x 0.5. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure for workers). For workers, the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under respective conditions (6.7 m³ for base level, 10 m³ for light activity). In addition, the NOAEL needs to be divided by 2 as the bioavailability via the inhalation route is considered as 100% while for oral exposure this is assumed to be 50%.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point
AF for differences in duration of exposure:
1
Justification:
The repeated dose toxicity study was conducted for 180 days and therefore considered chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
included in the route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.89 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
180
Dose descriptor starting point:
NOAEL
Value:
160 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL of 160 mg/kg/day established in the 21 -day repeated dose toxicity study (dermal route, OECD 410; Teuns, 1991) with the related substance imazalil was used to derive a DNEL long-term, systemic effects via the dermal route.

AF for dose response relationship:
1
Justification:
NOAEL is used as starting point
AF for differences in duration of exposure:
6
Justification:
difference in study duration subacute to chronic
AF for interspecies differences (allometric scaling):
2.4
Justification:
difference between rabbits and human
AF for other interspecies differences:
2.5
Justification:
default assessment factor
AF for intraspecies differences:
5
Justification:
Worker population
AF for the quality of the whole database:
1
Justification:
default assessment factor
AF for remaining uncertainties:
1
Justification:
default assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information
Explanation for the modification of the dose descriptor starting point:

The dermal acute exposure study (OECD 403 ; Moore, 1998 ) of rabbits to the test item lead to the Single Dose Acute Dermal LD50 of the test item is greater than 2000 mg/kg of bodyweight. The substance is considered not to be classified as acute dermal toxicant, based on the available data and according to the criteria laid down in the CLP Regulation (EC) 1272/2008, and is indicated to cause no hazard. The hazard categories are indicated in the Guidance on Information Requirements and Chemical Safety Assessment - Part E Risk Characterisation.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

No DNEL is derived for the general population, as no exposure is foreseen for this substance.