Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.35 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):
75
Dose descriptor starting point:
NOAEL
DNEL value:
126.4 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
176.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a developmental toxicity study in rabbits (similar to OECD 414, Qi, 2010). To correct the interspecies difference between rabbit and human the NOAEL has to be corrected as follows:

 Corrected inhal NOAEC = NOAEL(oral) × (1 ÷ sRVrabbit) × (ABSoral-rabbit ÷ ABSinh-human) × (sRVhuman ÷ wRV)

= 126.4 mg/kg bw/day × (1 ÷ 0.24 m³/kg bw) × (1 ÷ 2) × (6.7 m³ ÷ 10 m³) = 176.4 mg/m³

sRV = standard respiratory volume; wRV = respiratory volume light activity for worker (8 h); ABS = absorption

As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption.

Thus, the corrected starting point for workers is 176.4 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The available information is of adequate and reliable quality.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.7 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):
180
Dose descriptor starting point:
NOAEL
DNEL value:
126.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a developmental toxicity study in rabbits (similar to OECD 414, Qi, 2010).

To correct the interspecies difference between rabbit and human the NOAEL has to be corrected as follows:

Corrected dermal NOAEL = oral NOAEL × (ABSrabbit-oral ÷ ABShuman-dermal) = 126.4 mg/kg bw/day × (1 ÷ 1) = 126.4 mg/kg bw/day

The dermal absorption percentage was assumed to be 100% as no dermal data on long-term exposure is available.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default value according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The available information is of adequate and reliable quality.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

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:
0.56 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):
150
Dose descriptor starting point:
NOAEL
DNEL value:
126.4 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
87.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a developmental toxicity study in rabbits (similar to OECD 414, Qi, 2010).

To correct the interspecies difference between rabbit and human the NOAEL has to be corrected as follows:

Corrected inhal NOAEC = NOAEL(oral) × (1 ÷ sRVrabbit) × (ABSoral-rabbit ÷ ABSinh-human)

= 126.4 mg/kg bw/day × (1 ÷ 0.72 m³/kg bw) × (1 ÷ 2) = 87.8 mg/m³

As worst case as recommended in the ECHA Guidance R.8 (2012), it is assumed that oral absorption rate is 50% of that of inhalation absorption (ABS = absorption).

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The available information is of adequate and reliable quality.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.35 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):
360
Dose descriptor starting point:
NOAEL
DNEL value:
126.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a developmental toxicity study in rabbits (similar to OECD 414, Qi, 2010).

To correct the interspecies difference between rabbit and human the NOAEL has to be corrected as follows:

Corrected dermal NOAEL = oral NOAEL × (ABSrabbit-oral ÷ ABShuman-dermal) = 126.4 mg/kg bw/day × (1 ÷ 1) = 126.4 mg/kg bw/day

The dermal absorption percentage was assumed to be 100% as no dermal data on long-term exposure is available.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default value according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The available information is of adequate and reliable quality.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.35 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):
360
Dose descriptor starting point:
NOAEL
DNEL value:
126.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral absorption percentage was assumed to be 100%, based on the physicochemical data.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study.
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default value according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default value according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
The available information is of adequate and reliable qualtiy.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population