Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.212 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
2.645 mg/m³
AF for dose response relationship:
1
Justification:
Starting point NOAEC
AF for differences in duration of exposure:
1
Justification:
Based on carcinogenicity study
AF for interspecies differences (allometric scaling):
1
Justification:
Mouse
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.034 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
87.5
Dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A worst case scenario is assumed in which the absorption rate from dermal route is considered to be 100%.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
1
Justification:
Carcinogenicity study
AF for interspecies differences (allometric scaling):
7
Justification:
Mouse
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

As basis for DNEL derivation, the result from a 27-week carcinogenicity study in female p53 haploinsufficient mice via dermal route was used (NTP protocol, GLP study). This NOAEL of 3 mg/kg bw/d was selected as a worst case scenario, as it is the lowest available value and from the longest available study for this substance. Also as a worst-case scenario, dermal absorption was assumed to be 100%. All calculations were performed according to ECHA guidance documents.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.052 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
1.304 mg/m³
AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
1
Justification:
Carcinogenicity study
AF for interspecies differences (allometric scaling):
1
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default
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:
DNEL (Derived No Effect Level)
Value:
0.017 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):
175
Dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Starting point NOAEL
AF for differences in duration of exposure:
1
Justification:
Carcinogenicity study
AF for interspecies differences (allometric scaling):
7
Justification:
Mice
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.017 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
175
Dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
3 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
1
Justification:
Carcinogenicity study
AF for interspecies differences (allometric scaling):
7
Justification:
Mice
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (general population)
AF for the quality of the whole database:
1
Justification:
Default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

As basis for DNEL derivation, the result from a 27-week carcinogenicity study in female p53 haploinsufficient mice via dermal route was used (NTP protocol, GLP study). This NOAEL of 3 mg/kg bw/d was selected as a worst case scenario, as it is the lowest available value and from the longest available study for this substance. Also as a worst-case scenario, dermal absorption was assumed to be 100%. All calculations were performed according to ECHA guidance documents.