Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
235 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
3
Dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
705 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction of starting point from an oral study to the inhalative route according to Guidance on information requirements and chemical safety assessment Chapter R.8.4.2:

40 mg/kg bw/d *1/(0.38 m³/kg bw/d) * (6.7m³/10m³) = 70.5 mg/m3/d

A DINCH concentration in the gas phase higher than 0.5 μg/m3 is not achievable (Schossler et al, 2011; see IUCLID section 7.10.5). Thus, direct respiratory uptake of gaseous DINCH is considered negligible. In addition, in the rare case, DINCH uptake via the respiratory route occured, the vast majority of the uptake is expected to occur indirectly via dust-bound DINCH. According to in vitro data, the respiratory bioaccesibility of DINCH in indoor dust is less than 5% (Kadegoglou, 2018; see IUCLID section 7.1.1). Hence, in a worst case approach, the respiratory absorption of DINCH is considered to be 5% of the total substance-uptake. The oral absorption is considered to be 50% (see IUCLID section 7.1.1).

Taken together, the starting point was corrected as follows:

70.5 mg/m3/d x (50/5) = 705 mg/m3/d

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
3
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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
42 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
12
Dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is experimental data for the structurally closely related substance DINP (CAS# 68515-48-0), showing that less than 4% of the total applied substance is absorbed by the skin (EU RAR on DINP, 2003). DINCH has an even higher log Kow compared to DINP, making it even less favourable for dermal absorption. Therefore, in a worst case approach, the dermal absorption of DINCH is considered to be 4% of the total applied substance.

The oral absorption is considered to be 50% (see IUCLID section 7.1.1).

Correction of starting point:

NOAEL rat, oral x (Abs rat oral/Abs human dermal)

40 mg/kg bw/d x (50/4) = 500 mg/kg bw/d

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
3
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
70 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
5
Dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
350 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction of starting point from an oral study to the inhalative route according to Guidance on information requirements and chemical safety assessment Chapter R.8.4.2:

40 mg/kg bw/d *1/(1.15 m³/kg bw/d) = 35 mg/m3/d

A DINCH concentration in the gas phase higher than 0.5 μg/m3 is not achievable (Schossler et al, 2011; see IUCLID section 7.10.5). Thus, direct respiratory uptake of gaseous DINCH is considered negligible. In addition, in the rare case, DINCH uptake via the respiratory route occured, the vast majority of the uptake is expected to occur indirectly via dust-bound DINCH. According to in vitro data, the bioaaccessiblity of DINCH in indoor dust is less than 5% (Kadegoglou, 2018; see IUCLID section 7.1.1). Hence, in a worst case approach, the respiratory absorption of DINCH is considered to be 5% of the total substance-uptake.

The oral absorption is considered to be 50% (see IUCLID section 7.1.1).

Taken together, the starting point was corrected as follows:

35 mg/m3/d x (50/5) = 350 mg/m3/d

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
5
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
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:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
20
Dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is experimental data for the structurally closely related substance DINP (CAS# 68515 -48-0), showing that less than 4% of the total applied substance is absorbed by the skin (EU RAR on DINP, 2003). DINCH has an even higher log Kow compared to DINP, making it even less favourable for dermal absorption. Therefore, in a worst case approach, the dermal absorption of DINCH is considered to be 4% of the total applied substance.

The oral absorption is considered to be 50% (see IUCLID section 7.1.1).

Correction of starting point:

NOAEL rat, oral x (Abs rat oral/Abs human dermal)

40 mg/kg bw/d x (50/4) = 500 mg/kg bw/d

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
5
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:
2 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
20
Dose descriptor starting point:
NOAEL
Value:
40 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
1
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
5
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