Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.34 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEC
Value:
101.84 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation needed. Corrected inhalation NOAEL = oral rat NOAEL * (1/sRV rat) * (ABS oral rat/ABS inh hu) * (sRV human / wRV) = (400 mg/kg/d) * (0.38 m3/kg/d) * (ABS oral rat/ABS inh hu) * (6.7m3 (8h) / 10m3 (8h) = 101.84 mg/m3

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Duration is extrapolated from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8
AF for intraspecies differences:
5
Justification:
"For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill".
AF for the quality of the whole database:
1
Justification:
OECD TG 421 & GLP study
AF for remaining uncertainties:
1
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:
1.33 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No correction is needed on the assumption that, in general, dermal absorption won’t be higher than oral absorption.

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAECL
AF for differences in duration of exposure:
6
Justification:
Duration is extrapolated from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8
AF for intraspecies differences:
5
Justification:
As mentioned in ECHA Guidance R8 v2.1: "For workers, as standard procedure for threshold effects a default assessment factor of 5 is to be used, based on the fact that this sub population does not cover the very young, the very old, and the very ill".
AF for the quality of the whole database:
1
Justification:
OECD TG 421 & GLP study
AF for remaining uncertainties:
1
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.58 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEC
Value:
781.97 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation needed. Corrected inhalation NOAEL  = oral rat NOAEL * (1/sRV rat) * (ABS oral rat/ABS inh rat) * (ABS inh rat/ABS inh hu) = (400 mg/kg/d) * (1/1.15 m3/kg/d) * (ABS oral rat/ABS inh hu) = 347.82 mg/m3

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Duration is extrapolated from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8
AF for intraspecies differences:
10
Justification:
"it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
OECD TG 421 & GLP study
AF for remaining uncertainties:
1
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:
0.67 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No correction is needed on the assumption that, in general, dermal absorption won’t be higher than oral absorption.

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Duration is extrapolated from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8
AF for intraspecies differences:
10
Justification:
As mentioned in ECHA Guidance R8 v2.1: "it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
OECD TG 421 & GLP
AF for remaining uncertainties:
1
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:
0.67 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
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:
400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No correction is needed as starting route = ending route and there is no time-scaling correction.

AF for dose response relationship:
1
Justification:
Starting point for the DNEL calculation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Duration is extrapolated from sub-acute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
An AS factor of 4 for rat as compared to humans is presented in ECHA Guidance R8
AF for other interspecies differences:
2.5
Justification:
Default factor mentioned in ECHA Guidance R8
AF for intraspecies differences:
10
Justification:
As mentioned in ECHA Guidance R8 : "it is usually assumed that a default assessment factor of 10 is sufficient to protect the larger part of the population, including e.g. children and the elderly".
AF for the quality of the whole database:
1
Justification:
OECD TG 421 & GLP study
AF for remaining uncertainties:
1
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