Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.87 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
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
247 mg/m³
Explanation for the modification of the dose descriptor starting point:

results in most conservative DNEL

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.8 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
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
280 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

results in most conservative DNEL

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Selection of the relevant dose descriptors:

90 d NOAEL = 200 mg/kg bw/d (rat, OECD TG 408, oral study)

90 d NOAEC = 1000 mg/m³ (rat, OECD TG 413, inhalation study)

NOAEL(reproduction) = 1000 mg/kg bw/d (rat, OECD TG 422, screening study)

NOAEL(development) = 300 mg/kg bw/d (rat, OECD TG 414)

 

Modification of the relevant dose descriptors to the correct starting point: 

Oral absorption

The physicochemical properties of Oxooil LS9 (log Kow = 4.17; weighted mean) and the molecular weight of 114.23 g/mol are in a range suggestive of absorption from the gastro-intestinal tract subsequent to oral ingestion (molecular weight < 500 g/mol, log Kow between -1 and 4).

For chemical safety assessment an oral absorption rate of 50% is assumed as a worst case default value in accordance with Guidance on Information Requirements and Chemical Safety Assessment, R8.

 

Dermal absorption

The physicochemical properties of Oxooil LS9 (log Kow = 4.17; weighted mean) and the molecular weight of 114.23 g/mol are in a range suggestive of dermal absorption. For chemical safety assessment a dermal absorption rate of 50% is assumed as a worst case default value in accordance with Guidance on Information Requirements and Chemical Safety Assessment, R8.

 

Inhalation absorption

For chemical safety assessment an inhalation absorption rate of 100% is assumed as a worst case default value in accordance with Guidance on Information Requirements and Chemical Safety Assessment, R8.

 

DERIVATION OF DNELs

DNELs derived from the subchronic repeated dose toxicity NOAEL (OECD guideline 408)

 

Worker-DNEL long-term for inhalation route (systemic): 9.87 mg/m³

Start value: 200 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 247 mg/m³

 

For workers the corrected inhalation NOEC is calculated according to the following equation:

corrected inhalation NOAEC = oral NOAEL x 1/sRVrat x ABSoral-rat/ ABSinh-human x sRVhuman/ wRV x correction for exposure conditions (7 d / 5 d)

                                             = 200 x 1/0.38 x 50/100 x 6.7/10 x 1.4

The corrected inhalation NOAECworker (8h) is therefore:

                                             = 247 mg/m³ (8h-TWA)

 

Overall AF: 1*2*1*2.5*5*1*1 = 25

 

 

Worker-DNEL long-term for dermal route (systemic):  2.8 mg/kg bw/d

Start value: 200 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 280 mg/kg bw/d

 

corrected dermal NOAEL          = oral NOAEL x correction for exposure conditions (7 d / 5 d)

                                              = 200 x 1.4

                                               = 280 mg/kg bw/d

 

Overall AF: 1*2*4*2.5*5*1*1 = 100

 

 

DNELs derived from the 90 d inhalation toxicity study (inhalation route only)

Worker-DNEL long-term for inhalation route (systemic): 20.1 mg/m³

Start value: 1000 mg/m³

Route of original study: inhalation

 

corrected inhalation NOAEC = inhalation NOAEC x sRVhuman/ wRV x correction for exposure conditions (6 h / 8 h)

                                             = 1000 x 6.7/10 x 0.75

The corrected inhalation NOAECworker (8h) is therefore:

                                             = 502.5 mg/m³ (8h-TWA)

 

Overall AF: 1*2*1*2.5*5*1*1 = 25

 

The DNEL derived from the 90d oral study is more conservative and will be used as key value.

 

DNELs derived from the prenatal developmental toxicity study 

No time extrapolation is required for a prenatal developmental toxicity study, since the susceptible window is fully covered.

 

Worker-DNEL long-term for inhalation route (systemic): 21.1 mg/m³

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 264.32 mg/m³

 

For workers the corrected inhalation NOEC is calculated according to the following equation:

corrected inhalation NOAEC = oral NOAEL x 1/sRVrat x ABSoral-rat/ ABSinh-human x sRVhuman/ wRV x correction for exposure conditions (7 d / 5 d)

                                             = 300 x 1/0.38 x 50/100 x 6.7/10 x 1.4

The corrected inhalation NOAECworker (8h) is therefore:

                                             = 264.32 mg/m³ (8h-TWA)

 

Overall AF: 1*1*1*2.5*5*1*1 = 12.5

 

 

Worker-DNEL long-term for dermal route (systemic):  8.4 mg/kg bw/d

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 420 mg/kg bw/d

 

corrected dermal NOAEL          = oral NOAEL x correction for exposure conditions (7 d / 5 d)

                                              = 300 x 1.4

                                               = 420 mg/kg bw/d

 

Overall AF: 1*1*4*2.5*5*1*1 = 50

 

The DNELS derived from the oral subchronic toxicity study are also protective for developmental effects.

 

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.74 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
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:

results in most conservative DNEL

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

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

results in most conservative DNEL

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

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

results in most conservative DNEL

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
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

Selection of the relevant dose descriptors:

90 d NOAEL = 200 mg/kg bw/d (rat, OECD TG 408, oral study)

90 d NOAEC = 1000 mg/m³ (rat, OECD TG 413, inhalation study)

NOAEL(reproduction) = 1000 mg/kg bw/d (rat, OECD TG 422, screening study)

NOAEL(development) = 300 mg/kg bw/d (rat, OECD TG 414)

 

Modification of the relevant dose descriptors to the correct starting point: 

Oral absorption

The physicochemical properties of Oxooil LS9 (log Kow = 4.17; weighted mean) and the molecular weight of 114.23 g/mol are in a range suggestive of absorption from the gastro-intestinal tract subsequent to oral ingestion (molecular weight < 500 g/mol, log Kow between -1 and 4).

For chemical safety assessment an oral absorption rate of 50% is assumed as a worst case default value in accordance with Guidance on Information Requirements and Chemical Safety Assessment, R8.

 

Dermal absorption

The physicochemical properties of Oxooil LS9 (log Kow = 4.17; weighted mean) and the molecular weight of 114.23 g/mol are in a range suggestive of dermal absorption. For chemical safety assessment a dermal absorption rate of 50% is assumed as a worst case default value in accordance with Guidance on Information Requirements and Chemical Safety Assessment, R8.

 

Inhalation absorption

For chemical safety assessment an inhalation absorption rate of 100% is assumed as a worst case default value in accordance with Guidance on Information Requirements and Chemical Safety Assessment, R8.

 

DERIVATION OF DNELs

DNELs derived from the subchronic repeated dose toxicity NOAEL (OECD guideline 408)

 

General population-DNEL long-term for inhalation route (systemic): 1.74 mg/m³

Start value: 200 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 87.0 mg/m³

 

For general population the corrected inhalation NOEC is calculated according to the following equation:

corrected inhalation NOAEC  = oral NOAEL x 1/sRVrat x ABSoral-rat/ ABSinh-human

                                             = 200 x 1/1.15 x 50/100

 

The corrected inhalation NOAECgeneral population (24 h) is therefore:

                                             = 87.0 mg/m³ (24 h)

Overall AF: 1*2*1*2.5*10*1*1 = 50

 

 

general population-DNEL long-term for dermal route (systemic):  1 mg/kg bw/d

Start value: 200 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 200 mg/kg bw/d

Overall AF: 1*2*4*2.5*10*1*1 = 200

 

general population-DNEL long-term for oral route (systemic):  1 mg/kg bw/d

Start value: 200 mg/kg bw/d

Route of original study: oral

Overall AF: 1*2*4*2.5*10*1*1 = 200

 

DNELs derived from the 90 d inhalation toxicity study (inhalation route only)

 

General population-DNEL long-term for inhalation route (systemic): 3.6 mg/m³

Start value: 1000 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 178.6 mg/m³

 

For general population the corrected inhalation NOEC is calculated according to the following equation:

corrected inhalation NOAEC = inhalation NOAEC x correction for exposure conditions (6 h / 24 h x 5 d / 7 d)

                                             = 1000 x 6/24 x 5/7

 

The corrected inhalation NOAECgeneral population (24 h) is therefore:

                                             = 178.6 mg/m³ (24 h)

 

Overall AF: 1*2*1*2.5*10*1*1 = 50

 

 

The DNEL derived from the 90d oral study is more conservative and will be used as key value.

 

DNELs derived from the prenatal developmental toxicity study 

No time extrapolation is required for a prenatal developmental toxicity study, since the susceptible window is fully covered.

 

General population-DNEL long-term for inhalation route (systemic): 5.2 mg/m³

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 130.5 mg/m³

 

For general population the corrected inhalation NOEC is calculated according to the following equation:

corrected inhalation NOAEC  = oral NOAEL x 1/sRVrat x ABSoral-rat/ ABSinh-human

                                             = 300 x 1/1.15 x 50/100

 

The corrected inhalation NOAECgeneral population (24 h) is therefore:

                                             = 130.5 mg/m³ (24 h)

Overall AF: 1*1*1*2.5*10*1*1 = 25

 

 

general population-DNEL long-term for dermal route (systemic):  3 mg/kg bw/d

Start value: 300 mg/kg bw/d

Route of original study: oral

Dose descriptor starting point after route-to-route extrapolation: 300 mg/kg bw/d

Overall AF: 1*1*4*2.5*10*1*1 = 100

 

general population-DNEL long-term for oral route (systemic):  3 mg/kg bw/d

Start value: 300 mg/kg bw/d

Route of original study: oral

Overall AF: 1*1*4*2.5*10*1*1 = 100

 

The DNELS derived from the oral subchronic toxicity study are also protective for developmental effects.