Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.24 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
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
881.05 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is required for oral to inhalation route as there is no long-term inhalation study available.

The dose descriptor starting point was the NOAEL of 1000 mg/kg bw/day for general systemic toxicity, obtained from a combined one-generation reproduction/sub-chronic toxicity study in rats (OECD 408 & 415).

The corrected dose descriptor (NOAEC) for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health. It is assumed that oral absorption of the substance is half that of inhalation absorption.

The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for workers (assuming an 8-hour exposure/day).

Inhalatory N(L)OAEC = oral N(L)OAEL*(1/0.38 m3/kg/d)*0.67*(ABSoral/ABSinh.)

= 1000 * 2.63 * 0.67 * 0.5

= 881.05 mg/m3

AF for dose response relationship:
1
Justification:
As the dose descriptor is the NOAEL, the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
To account for using PoD taken from a subchronic study to calculate a chronic DNEL.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is usually not applied in the derivation of the inhalation DNEL.
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
To account for intraspecies differences in an occupational setting.
AF for the quality of the whole database:
1
Justification:
The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties identified therefore not applicable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.24 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
DNEL extrapolated from long term DNEL

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:
10 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
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation is required for oral to dermal route as there is no long-term dermal study available.

The dose descriptor starting point was the NOAEL of 1000 mg/kg bw/day for general systemic toxicity, obtained from a combined one-generation reproduction/sub-chronic toxicity study in rats (OECD 408 & 415).

The corrected dose descriptor (NOAEL) for dermal exposure was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected dermal NOAEL to assess human dermal exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for workers (assuming an 8-hour exposure/day).

Dermal N(L)OAEL=oral (N(L)OAEL*( ABSoral/ABSdermal)

                = 1000 x (1/1)

AF for dose response relationship:
1
Justification:
As the dose descriptor is the NOAEL, the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
To account for using PoD taken from a subchronic study to calculate a chronic DNEL.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to account for differences in allometry in using the rat as a test model.
AF for other interspecies differences:
2.5
Justification:
Default factor.
AF for intraspecies differences:
5
Justification:
To account for intraspecies differences in an occupational setting.
AF for the quality of the whole database:
1
Justification:
The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties identified therefore not applicable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 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
DNEL extrapolated from long term DNEL

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:
8.69 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
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
434.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

In the absence of a repeated dose toxicity study conducted via the inhalation route of exposure the use of a PoD using the oral route of exposure has been employed. The NOAEL is taken from repeat dose oral toxicity studies in rats. It is assumed that oral absorption of the substance is half that of inhalation absorption.

 

Inhalatory N(L)OAEC = oral N(L)OAEL*(1/1.15 m3/kg bw/d)*(ABSoral/ABSinh.)

= 1000 * 0.869 * 0.5

= 434.5 mg/m3

AF for dose response relationship:
1
Justification:
As the dose descriptor is the NOAEL, the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
To account for using PoD taken from a subchronic study to calculate a chronic DNEL.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is usually not applied in the derivation of the inhalation DNEL.
AF for other interspecies differences:
2.5
Justification:
Default factor.
AF for intraspecies differences:
10
Justification:
To account for intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties identified therefore not applicable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.69 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
DNEL extrapolated from long term DNEL

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:
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
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the absence of a repeated dose toxicity study conducted via the dermal route of exposure the use of a PoD using the oral route of exposure has been employed. The dose descriptor starting point was the NOAEL of 1000 mg/kg bw/day for general systemic toxicity, obtained from a combined one-generation reproduction/sub-chronic oral toxicity study in rats (OECD 408 & 415).

The corrected dose descriptor (NOAEL) for dermal exposure was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected dermal NOAEL to assess human dermal exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for the general population.

Dermal N(L)OAEL=oral (N(L)OAEL*( ABSoral/ABSdermal)

                = 1000 x (1/1)

AF for dose response relationship:
1
Justification:
As the dose descriptor is the NOAEL, the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
To account for using PoD taken from a subchronic study to calculate a chronic DNEL.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to account for differences in allometry in using the rat as a test model.
AF for other interspecies differences:
2
Justification:
Default factor.
AF for intraspecies differences:
10
Justification:
To account for intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties identified therefore not applicable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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
Dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
As the dose descriptor is the NOAEL, the default assessment factor is 1.
AF for differences in duration of exposure:
2
Justification:
To account for using PoD taken from a subchronic study to calculate a chronic DNEL.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to account for differences in allometry in using the rat as a test model.
AF for other interspecies differences:
2.5
Justification:
Default factor.
AF for intraspecies differences:
10
Justification:
To account for intraspecies differences.
AF for the quality of the whole database:
1
Justification:
The database has a good quality, taking into account completeness, consistency and the standard information requirements, therefore the default factor of 1 applies.
AF for remaining uncertainties:
1
Justification:
There are no remaining uncertainties identified therefore not applicable.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
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
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

There are no identified uses in the public domain however DNEL values for the General Population have been calculated to support the assessment of man via the environment.