Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.21 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):
25
Modified dose descriptor starting point:
other: NOAEC corrected
DNEL value:
5.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAECcorr = NOAELoral*(1/0.38 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)) = 2.97 mg/kg bw/day*(1/0.38 m³/kg bw/day)*0.67= 5.2 mg/m³. It is assumed that oral absorption rate is 100% of that of the inhalation absorption.
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a subchronic study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF for workers
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.3 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):
300
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF for workers
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

No quantitative dose-response data are available for local effects on skin and respiratory tract. The most sensitive local endpoint is skin sensitisation (Vohr, 2005).

 

The long-term worker DNEL for dermal systemic effects is based on the 28-day dermal study in rats, with NOAEL = 1000 mg/kg bw/day (Eigenberg, 2009). When a route-specific study is available, this is the preferred choice to derive the DNEL.

The long-term worker DNEL for inhalation systemic effects is based on the 2-generation reproduction toxicity feeding study in rats, with NOAEL = 2.97 mg/kg bw/day (Aoyama, 2007). This study was chosen as the starting point for deriving the DNEL as it has the lowest NOAEL for systemic effects of the available oral repeated dose studies and as there is no inhalation repeated dose study. The starting point was corrected using the 10 m³ breathing volume per 8-h shift with light physical activity. The absorption was assumed to be 100% for oral and inhalation exposure, as there were no differences in effects between the acute oral and inhalation studies. Therefore the assessment factor for absorption is set as 1.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The general population is not exposed to the test substance, based on its identified uses.