Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.53 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):
75
Modified dose descriptor starting point:
NOAEC
DNEL value:
264.32 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAECcorr = NOAELoral*(1/0.38 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)) = 300 mg/kg bw/day*(1/0.38 m³/kg bw/day)*(0.5/1)*0.67 = 264.32 mg/m³. It is assumed that dermal absorption rate is 50% of that of inhalation absorption. ABSoral-rat=oral absorption rate in rats, ABSinh-human=inhalation absorption rate in humans. Adverse effects were seen in the available subacute oral study at the highest concentration/dose level tested. Therefore, the NOAEL (300 mg/kg bw/day) from this subacute oral toxicity study was the most sensitive effect level and was selected for DNEL derivation by means of route-to-route extrapolation.
AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a 28-d study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF for workers
AF for the quality of the whole database:
1
Justification:
The selected study is the moste adequate and reliable study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainities
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:
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
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAELcorr = NOAELoral*(ABSoral-rat/ABSdermal-human) = (300 mg/kg bw/day)*(0.5/0.1) = 1500 mg/kg bw/day. It is assumed that the dermal absorption rate is 10% (20% of that of the oral absorption) based on the available data and physico-chemical properties of the PFAE aromatic category members (high MW, very high LogPow, very low water solubility)according to ECHA CSA Guidance Chapter R.7c. ABSoral-rat=oral absorption rate in rats, ABSdermal-human=dermal absorption rate in humans.
AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a 28-d study
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF for workers
AF for the quality of the whole database:
1
Justification:
The selected study is the most adequate and reliable study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainities
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

The long-term DNELs are based on a 28-day oral feeding study performed in Sprague Dawley rats with 1,2,4-Benzenetricarboxylic acid, decyl octyl ester (CAS 90218-76-1) as a Read Across substance. The NOAEL in this study was found to be 300 mg/kg bw/day based on systemic effects (reduced body weight, males; hair loss, females; increased leucocytes, females and (reversible) effects on adrenals and liver) at the highest dose of 1000 mg/kg bw/day. In another 28-day oral feeding study performed withTris(2-ethylhexyl) benzene-1,2,4-tricarboxylate (CAS No. 3319-31-1), a surrogate substance, no adverse effects were observed up to the highest dose of 1000 mg/kg bw/day. The long-term systemic DNELs were derived based on the most sensitive NOAEL being 300 mg/kg bw/day.

As the DNELs were derived for the whole category, no adaption regarding the molecular weight was done. However, the Read Across substance tested in the respective study is the category member with the lowest molecular weight und thus, the derived DNELs can be seen as the worst case calculation with regard to the other category members.

The assessment factors were chosen according to ECHA Guidance document R.8 (Characterisation of dose [concentration]-response for human health, May 2008.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 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):
150
Modified dose descriptor starting point:
NOAEC
DNEL value:
130.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAECcorr = NOAELoral*(1/1.15 m³/kg bw/day)*(ABSoral-rat/ABSinh-human) = 300 mg/kg bw/day*(1/1.15 m³/kg bw/day)*(0.5/1) = 130.5 mg/m³. It is assumed that dermal absorption rate is 50% of that of inhalation absorption. ABSoral-rat=oral absorption rate in rats, ABSinh-human=inhalation absorption rate in humans. No adverse effects were seen in the available subacute inhalation study and the subacute and subchronic oral studies up to and including the highest concentration/dose level tested. Therefore, the lowest dose descriptor from the study with the longest duration, i.e. the NOAEL from the subchronic oral toxicity study, was selected for DNEL derivation by means of route-to-route extrapolation.
AF for dose response relationship:
1
Justification:
DNEL is basedon a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a 28-day study
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
1
Justification:
The selected study is the most adequate and reliable study.
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:
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:
2.5 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):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAELcorr = NOAELoral*(ABSoral-rat/ABSdermal-human) = (300 mg/kg bw/day)*(0.5/0.1) = 1500 mg/kg bw/day. It is assumed that the dermal absorption rate is 10% (20% of that of the oral absorption) based on the available data and physico-chemical properties of the PFAE aromatic category members (high MW, very high LogPow, very low water solubility)according to ECHA CSA Guidance Chapter R.7c. ABSoral-rat=oral absorption rate in rats, ABSdermal-human=dermal absorption rate in humans.
AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a 28-d study
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
1
Justification:
The selected study is the moste adequate and reliable study.
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:
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:
0.5 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):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation is required.
AF for dose response relationship:
1
Justification:
DNEL is based on a NOAEL
AF for differences in duration of exposure:
6
Justification:
DNEL is based on a 28-day study
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for rats
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
1
Justification:
The selected study is the most adequate and reliable study.
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

The long-term DNELs are based on a 28-day oral feeding study performed in Sprague Dawley rats with 1,2,4-Benzenetricarboxylic acid, decyl octyl ester (CAS 90218-76-1) as a Read Across substance. The NOAEL in this study was found to be 300 mg/kg bw/day based on systemic effects (reduced body weight, males; hair loss, females; increased leucocytes, females and (reversible) effects on adrenals and liver) at the highest dose of 1000 mg/kg bw/day. In another 28-day oral feeding study performed withTris(2-ethylhexyl) benzene-1,2,4-tricarboxylate (CAS No. 3319-31-1), a surrogate substance, no adverse effects were observed up to the highest dose of 1000 mg/kg bw/day. The long-term systemic DNELs were derived based on the most sensitive NOAEL being 300 mg/kg bw/day.

As the DNELs were derived for the whole category, no adaption regarding the molecular weight was done. However, the Read Across substance tested in the respective study is the category member with the lowest molecular weight und thus, the derived DNELs can be seen as the worst case calculation with regard to the other category members.

The assessment factors were chosen according to ECHA Guidance document R.8 (Characterisation of dose [concentration]-response for human health, May 2008.