Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.099 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
BMDL10
Value:
2.8 mg/kg bw/day
Modified dose descriptor starting point:
BMCL10
Value:
2.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

The point of departure is based on a 2 -generation reproductive toxicity study with TPP (CAS 121158 -58 -5). The NOAEL was 1.5 mg/kg bw/day based on renal mineralization that occurred 15 mg/kg bw/day; reproductive toxicity (effects on fertility) had a NOAEL of 15 mg/kg bw/day. A BMDL of 2.8 mg/kg bw/day was calculated and taken as the starting point. Oral to inhalation was corrected by applying the following equation: ((1/sRvrat(0.38))X(ABSoral-rat(50)/ABSinh-human(100))X(sRVhumans(6.7)/wRV(10))).

AF for dose response relationship:
1
Justification:
ECHA REACH guidance
AF for differences in duration of exposure:
2
Justification:
Based on 2-generation study
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH guidance
AF for the quality of the whole database:
1
Justification:
High quality and robust data set available
AF for remaining uncertainties:
1
Justification:
ECHA guidance
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:
0.47 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
BMDL10
Value:
2.8 mg/kg bw/day
Modified dose descriptor starting point:
BMDL10
Value:
47 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on dermal absorption data (see EC 272 -234 -3/701 -251 -5 REACH registration for full justification; also supported by ECHA conclusion document (28 February 2019)), the following equation is applied:

BMDL X 0.5 (oral abs) / 0.03 (dermal abs)

AF for dose response relationship:
1
Justification:
ECHA guidance
AF for differences in duration of exposure:
2
Justification:
2-generation reproductive toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA guidance
AF for other interspecies differences:
2.5
Justification:
ECHA guidance
AF for intraspecies differences:
5
Justification:
ECHA guidance
AF for the quality of the whole database:
1
Justification:
Robust database
AF for remaining uncertainties:
1
Justification:
No additional 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The risk assessment is conducted on TPP, which is an impurity in the notified substance. The DNELs are dervied for TPP and the exposure to the registered substance is adjusted based on the amount of residual TPP.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.024 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
BMDL10
Value:
2.8 mg/kg bw/day
Modified dose descriptor starting point:
BMCL10
Value:
1.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

The point of departure is based on a 2 -generation reproductive toxicity study with TPP (CAS 121158 -58 -5). The NOAEL was 1.5 mg/kg bw/day based on renal mineralization that occured 15 mg/kg bw/day; reproductive toxicity (effects on fertility) had a NOAEL of 15 mg/kg bw/day. A BMDL of 2.8 mg/kg bw/day was calculated and taken as the starting point. Oral to inhalation was corrected by applying the following equation: ((1/sRvrat(1.15))X(ABSoral-rat(50)/ABSinh-human(100)).

AF for dose response relationship:
1
Justification:
ECHA guidance
AF for differences in duration of exposure:
2
Justification:
2-generation reproductive toxicity study
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA guidance
AF for other interspecies differences:
2.5
Justification:
ECHA guidance
AF for intraspecies differences:
10
Justification:
ECHA guidance
AF for the quality of the whole database:
1
Justification:
High qualtity robust database
AF for remaining uncertainties:
1
Justification:
No additional 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:
0.24 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
BMDL10
Value:
2.8 mg/kg bw/day
Modified dose descriptor starting point:
BMDL10
Value:
560 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Based on dermal absorption data (see EC 272 -234 -3/701 -251 -5 REACH registration for full justification; also supported by ECHA conclusion document (28 February 2019)), the following equation is applied:

BMDL X 0.5 (oral abs) / 0.03 (dermal abs)

AF for dose response relationship:
1
Justification:
ECHA guidance
AF for differences in duration of exposure:
2
Justification:
2-generation reproductive toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA guidance
AF for other interspecies differences:
2.5
Justification:
ECHA guidance
AF for intraspecies differences:
10
Justification:
ECHA guidance
AF for the quality of the whole database:
1
Justification:
HIgh quality robust database
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:
0.014 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Dose descriptor starting point:
BMDL10
Value:
2.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No modifications

AF for dose response relationship:
1
Justification:
ECHA guidance
AF for differences in duration of exposure:
2
Justification:
2-generation reproductive toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA guidance
AF for other interspecies differences:
2.5
Justification:
ECHA guidance
AF for intraspecies differences:
10
Justification:
ECHA guidance
AF for the quality of the whole database:
1
Justification:
High quality robust database
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 risk assessment is conducted on TPP, which is an impurity in the notified substance. The DNELs are dervied for TPP and the exposure to the registered substance is adjusted based on the amount of residual TPP.