Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.242 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:
NOAEC
DNEL value:
881.05 mg/m³
Explanation for the modification of the dose descriptor starting point:
There is no repeated dose inhalation data. Therefore the repeated dose oral data has been used.
AF for dose response relationship:
1
Justification:
starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Not typically applied in the derivation of an inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
Default values
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
1
Justification:
good data base with a subchronic study of 2014 under GLP
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties 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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 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):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
5 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is no repeated dose dermal data. Therefore the repeated dose oral data has been used. The default value for oral absorption is 100 %, based on the dermal absorption rate of 10 % (molecular weight > 500; log KOW > 4) the dermal NOAEL is calculated 5000 mg/kg bw/d.
AF for dose response relationship:
1
Justification:
starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
good data base with a subchronic study of 2014 under GLP
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The most appropriate endpoint for derivation of a DNEL is the rat subchronic oral NOAEL of 500 mg/kg bw/d taken from a well conducted subchronic toxicity study. Based on the acute toxicity data, DNELs don't need to be derived for local or systemic effects for the worker population since the material has a low potential for acute toxicity.

Worker long term exposure - systemic effects (dermal):

DNELs were calculated from the oral NOAEL, assuming a 100 % oral absorption rate and a 10 % dermal absorption rate ( Molecular weight is > 500 and log POW > 4) ( REACH guidance R7c, Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance, November 2012, page 199). The value of 5000 mg/kg bw/d (calculated dermal NOAEL) was divided by an adjustment factor of 100 (exposure duration factor of 2, interspecies factor of 4, additional allometric scaling 2.5 and intraspecies (worker population) factor of 5), leading to a DNEL of 50 mg/kg/d.

Worker long term exposure - systemic effects (inhalative):

The corrected worker inhalation starting point was the corrected NOAEC of 881.05 mg/m3 and was derived from the oral NOAEL of 500 mg/kg/d by multiplying by the inverse of the standard respiratory volume of the rat during an 8 hour period (2.63) and multiplied by the ratio of standard respiratory volume for humans to the 8 hour worker standard respiratory volume (0.67). The corrected starting point was adjusted by a factor of 25, resulting in a calculated DNEL of 35.242 mg/m3.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.7 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):
50
Modified dose descriptor starting point:
NOAEC
DNEL value:
435 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation study available. Therefore the repeated dose oral data has been used.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
subchronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Not typically applied in the derivation of an inhalation DNEL
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
good data base with a subchronic study of 2014 under GLP
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties 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:
DNEL (Derived No Effect Level)
Value:
25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
5 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No dermal study available. Therefore the repeated dose oral data has been used. The default value for oral absorption is 100 %, based on the dermal absorption rate of 10 % (molecular weight > 500; log KOW > 4) the dermal NOAEL is calculated 5000 mg/kg bw/d.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
good data base with a subchronic study of 2014 under GLP
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties 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:
DNEL (Derived No Effect Level)
Value:
2.5 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):
200
Modified dose descriptor starting point:
NOAEL
DNEL value:
500 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Justification:
good data base with a subchronic study of 2014 under GLP
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties 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

The most appropriate endpoint for derivation of a DNEL is the rat oral NOAEL of 500 mg/kg bw/d taken from a well conducted subchronic toxicity study. Based on the acute toxicity data, DNELs don't need to be derived for local or systemic effects for the general population since the material has a low potential for acute toxicity.

General population long term exposure - systemic effects (oral)):

DNELs were calculated from the oral NOAEL. The value was divided by an adjustment factor of 200 (exposure duration factor of 2, interspecies factor of 4, allometric scaling 2.5 and intraspecies (general population) factor of 10), leading to a DNEL of 2.5 mg/kg/d.

General population long term exposure - systemic effects (dermal):

DNELs were calculated from the oral NOAEL, assuming a 100% oral absorption rate and a 10 % dermal absorption rate ( Molecular weight is > 500 and log POW > 4) ( REACH guidance R7c, Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance, November 2012, page 199).

The value of 5000 mg/kg bw/d (calculated dermal NOAEL) was divided by an adjustment factor of 200 (exposure duration factor of 2, interspecies factor of 4, allometric scaling 2.5 and intraspecies (general population) factor of 10), leading to a DNEL of 25 mg/kg/d.

General population long term exposure - systemic effects (inhalative)

The corrected general population inhalation starting point was the corrected NOAEC of 435 mg/m3 and was derived from the oral subchronic NOAEL of 500 mg/kg/d by multiplying by the inverse of the standard respiratory volume of the rat during a 24 hour period (0.87). The corrected starting point was adjusted by a factor of 50 resulting in a calculated DNEL of 8.7 mg/m3.