Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.5 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):
300
Dose descriptor starting point:
NOAEL
Value:
134.6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 346.2 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.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default rat
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default workers
AF for the quality of the whole database:
1
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

No data on repeated dose toxicity exists for the submission substance. However adequate and reliable data for a structural anologue is avialble (i.e. C8TM, RA based on structural similarity which is supported by comparable profile of physical-chemical properties; for further details on read-across justification please see read-across report in section 13).

There is only one study available with repeated dose administration. Thus the worker dermal DNEL for systemic effects and long-term exposure was derived by route-to-route extrapolation on basis of this combined repeated dose toxicity study with reproductive/developmental screening (subacute oral study, OECD 422, GLP conform) with a structural analogue of the submission substance in rats. Effects on clinical chemistry parameters were observed and the NOAEL was identified to be 125 mg/kg bw/day, which was corrected for molecular weight to 134.6 mg/kg bw/d. As this study was conducted via oral gavage route-to-route extrapolation is necessary. 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 to be 1346.2 mg/kg bw/day.

Using the default assessment factors as given in ECHA Guidance on information requirements and saftey assessment Chapter R.8 (interspecies rat AF4, interspecies remaining differences AF2.5, intraspecies workers AF5, exposure duration subacute to subchronic AF6 - overall AF: 300) the dermal DNEL for systemic effects and long-term exposure was calculated to be 4.5 mg/kg bw/day.

This DNEL derivation is judged to be a conservative approach as already the dose descriptor used for derivation represents a conservative value (effects observed on which the NOAEL was established are only borderline adverse). This conservative approach was chosen, based on the little data available.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.24 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
Dose descriptor starting point:
NOAEL
Value:
134.6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 346.2 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.
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default rat
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
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:
0.224 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
Dose descriptor starting point:
NOAEL
Value:
134.6 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
subacute to chronic
AF for interspecies differences (allometric scaling):
2.5
Justification:
default
AF for other interspecies differences:
4
Justification:
default rat
AF for intraspecies differences:
10
Justification:
default general population
AF for the quality of the whole database:
1
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

No data on repeated dose toxicity exists for the submission substance. However adequate and reliable data for a structural anologue is avialble (i.e. C8TM, RA based on structural similarity which is supported by comparable profile of physical-chemical properties; for further details on read-across justification please see read-across report in section 13).

There is only one study available with repeated oral dose administration.

Thus the general population dermal DNEL for systemic effects and long-term exposure was derived by route-to-route extrapolation on basis of this combined repeated dose toxicity study with reproductive/developmental screening (subacute oral study, OECD 422, GLP conform) with a structural analogue of the submission substance in rats. Effects on clinical chemistry parameters were observed and the NOAEL was identified to be 125 mg/kg bw/day, which was corrected for molecular weight to 134.6 mg/kg bw/d. As this study was conducted via oral gavage route-to-route extrapolation is necessary. 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 to be 1346.2 mg/kg bw/day.

Using the default assessment factors as given in ECHA Guidance on information requirements and saftey assessment Chapter R.8 (interspecies rat AF4, interspecies remaining differences AF2.5, intraspecies general population AF10, exposure duration subacute to subchronic AF6 - overall AF: 600) the dermal DNEL for systemic effects and long-term exposure was calculated to be 2.24 mg/kg bw/day.

The general population oral DNEL for systemic effects and long-term exposure was based on the same study with a corrected NOAEL for molecular weight being 134.6 mg/kg bw/day.

Using the default assessment factors as given in ECHA Guidance on information requirements and saftey assessment Chapter R.8 (interspecies rat AF4, interspecies remaining differences AF2.5, intraspecies general population AF10, exposure duration subacute to subchronic AF6 - overall AF: 600) the general population oral DNEL for systemic effects and long-term exposure was calculated to be 0.224 mg/kg bw/day.

These DNEL derivations are judged to be a conservative approach as already the dose descriptor used for derivation represents a conservative value (effects observed on which the NOAEL was established are only borderline adverse). This conservative approach was chosen, based on the little data available.

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