Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
76.3 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
7 630.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation factors, but dose modifiers are applied to the NOAEL from the rat study. Skin absorption rates were found to differ between rats and humans in toxicokinetic studies. A dose descriptor modifier of 2.7 was applied to account for the rate of dermal absorption in female rats (0.17 mg/cm2/h) compared with female human abdominal skin (0.07 mg/cm2/h). Additionally, the exposure period in the in vivo experimental study was 6 h, whereas a worker is potentially exposed for 8 h, a factor of 0.75.
AF for dose response relationship:
1
Justification:
Dose-response is demonstrated in experimental studies
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remainder (pharmacodynamic)
AF for intraspecies differences:
5
Justification:
individual variability
AF for the quality of the whole database:
1
Justification:
adequate
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
228.9 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):
0.33
DNEL extrapolated from long term DNEL

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
38.2 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
7 630.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation factors, but dose modifiers are applied to the NOAEL from the rat study. Skin absorption rates were found to differ between rats and humans in toxicokinetic studies. A dose descriptor modifier of 2.7 was applied to account for the rate of dermal absorption in female rats (0.17 mg/cm2/h) compared with female human abdominal skin (0.07 mg/cm2/h). Additionally, the exposure period in the in vivo experimental study was 6 h, whereas a worker is potentially exposed for 8 h, a factor of 0.75.
AF for dose response relationship:
1
Justification:
Dose-response is demonstrated in experimental studies
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remainder (pharmacodynamic)
AF for intraspecies differences:
10
Justification:
individual variability among the general population
AF for the quality of the whole database:
1
Justification:
adequate
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
114.5 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):
0.33
DNEL extrapolated from long term DNEL

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation was performed.
AF for dose response relationship:
1
Justification:
Dose-response is demonstrated in experimental studies
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
remainder (pharmacodynamic)
AF for intraspecies differences:
10
Justification:
individual variability
AF for the quality of the whole database:
1
Justification:
adequate
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.51 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
0.33
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population