Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
76 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 080 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

The long-term DNELs are based on a 28 -day oral feeding study performed in Alpk:APfSD rats with Fatty acids, C5-10, esters with pentaerythritol (CAS-No. 68424-31-7) as a Read Across substance. The NOAEL in this study was found to be 12500 ppm (1450 mg/kg bw/d for male and 1613 mg/kg bw/d for female rats, highest dose tested).

With regard to the molecular weight ratio of both substances and in a worst case assumption (male NOAEL and highest possible molecular weight for CAS-No. 68424-31 -7), the NOEL used for the calculation of DNELs was adapted for CAS No. 85116 -93 -4.

 

The molecular weight of Fatty acids, C16-18, esters with pentaerythritol (CAS No. 85116-93-4) is 1202.02 g/mol, the molecular weight of PE/DiPE ester of C5/C7/C8/C10 fatty acids(CAS No. 68424-31-7) is 472.62 - 753.2 g/mol.

 

An conversion factor of 1202.02 g/mol/753.2 g/mol = 1.6 was applied.

 

NOAEL(oral) (CAS-No. 85116-93-4) = NAOEL(oral) (CAS-No. 68424-31-7) x1.6

= 1450 mg/kg bw/d x 1.6 =2314 mg/kg bw/d. This value was used as basis for DNEL (systemic, long term) -calculation.

Route to route extrapolation (oral to inhalative) was performed according to the ECHA guidance document R.8 (characterization of dose[concentration]-response for human health). The exposition of the test animals was given on 7 days a week. For workers, the expected exposition is only 5 days a week. Therefore, a factor of 7/5 was introduced for workers due to the reduced exposition (working time of 5 days a week).

For workers:

corrected starting point (worker, inhalative) = oral NOAEL * 1/sRVrat* sRVhuman/wRV *7/5

= 2314 mg/kg bw/d/0.38 m3/kg bw/d*6.7m3/10m3*7/5 = 5711.9 mg/m3/d

corrected starting point (worker, oral) = oral NOAEL * 7/5 = 2314 mg/kg bw/d *7/5 = 3239.6 mg/kg bw/d

corrected starting point (worker, dermal) = oral NOAEL * 7/5 /0.01 = 2314 mg/kg bw/d/0.01 *7/5 = 323960.0 mg/kg bw/d

Due to the physicochemical properties of the test substance, only limited dermal absorption is expected (high molecular weight, poor water solubility and log Kow>4). Therefore a factor of 0.01 (1% absorption) for the difference in absorption was introduced.

For the calculation of the DNEL, the following safety factors were applied on the corrected starting points:

Dermal DNEL: Allometric scaling factor 4; interspecies factor 2.5; intraspecies factor 5; exposure duration factor 6; dose-response factor 1; quality of the database 1 = 300

Inhalation DNEL: Interspecies factor 2.5; intraspecies factor 5; exposure duration factor 6; dose-response factor 1; quality of the database 1 = 75

Taken together, the resulting dermal DNEL for workers is 1080 mg/kg bw/d, the inhalative DNEL is 76 mg/m3, respectively.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
LOAEC
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
386 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.9 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The calculation of the corrected starting points for the general population was as follows: For the general population (GP):

corrected starting point (GP, inhalative) = oral NOAEL * 1/sRVrat= 2314 mg/kg bw/d/1.15 m3/kg/d = 2012.2 mg/m3/d

corrected starting point (GP, oral) = oral NOAEL = 2314.0 m3/kg/d

corrected starting point (GP, dermal) = oral NOAEL/0.01 = 231400.0 m3/kg/d

Due to the physicochemical properties of the test substance, only limited dermal absorption is expected. Therefore, a factor of 0.01 (1% absorption) for the difference in absorption was introduced.

The DNEL calculation for the general population was performed equally as for the workers. In deviation to that, the assessment factor for intraspecies variability was set to 10 to account for more variability in the general population.

Resulting from this considerations, the DNELs calculated were 385.7 mg/kg bw/d, 3.9 mg/kg bw/d and 13.4 mg/m3 for dermal exposure, oral exposure and inhalation, respectively.