Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.67 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
LOAEC
Value:
100 mg/m³
Modified dose descriptor starting point:
LOAEC
Value:
50.25 mg/m³
Explanation for the modification of the dose descriptor starting point:
LOAEC instead of a NOAEC is chosen as a dose descriptor starting point. Rationale: (1) large spacing, factor 20, between LOAEC (100 mg/m3) and NOAEC (5.3 mg/m3) (2) the nature and incidence of the observed effects at the LOAEC. Corrected LOAEC = inhalatory LOAEC * 6 h/d / 8 h/d * 6.7 m3 (8h) / 10 m3 (8h) = inhalatory LOAEC * 0.503 = 50.25 mg/m3
AF for dose response relationship:
3
Justification:
AF for the use of a LOAEC instead of a NOAEC as dose descriptor starting point.
AF for differences in duration of exposure:
2
Justification:
AF for subchronic to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Not used for inhalation route.
AF for other interspecies differences:
2.5
Justification:
AF for potential remaining differences.
AF for intraspecies differences:
5
Justification:
AF for intraspecies differences for workers.
AF for the quality of the whole database:
1
Justification:
read-across to formulation with DBPP (Skydrol 500B-4) but this formulation is expected to be more harmful, as the levels of TBP are higher.
AF for remaining uncertainties:
1
Justification:
No additional uncertainties identified.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.67 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor:
other: Modified dose descriptor (LOAEL) consistent to the systemic route.
Value:
50.25 mg/m³
AF for dose response relationship:
3
Justification:
AF for the use of a LOAEC instead of a NOAEC as dose descriptor starting point.
AF for differences in duration of exposure:
2
Justification:
AF for subchronic to chronic.
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
AF for potential remaining differences.
AF for intraspecies differences:
5
Justification:
AF for intraspecies differences for workers
AF for the quality of the whole database:
1
Justification:
No additional AF required.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
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:
1.39 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
720
Dose descriptor starting point:
LOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The LOAEL instead of NOAEL is used as starting dose descriptor due to the tenfold difference between the NOAEL (100 mg/kg bw) and LOAEL (1000 mg/kg bw). The only observed systemic effect at the LOAEL was a decreased choline esterase activity.
AF for dose response relationship:
3
Justification:
Default AF for use of LOAEL.
AF for differences in duration of exposure:
8
Justification:
21-day study (15 days of treatment); AF for subacute * 28/21 = 8
AF for interspecies differences (allometric scaling):
2.4
Justification:
AF for allometric scaling from rabbit.
AF for other interspecies differences:
2.5
Justification:
AF for remaining differences.
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers.
AF for the quality of the whole database:
1
Justification:
No additional AF required.
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:
DNEL (Derived No Effect Level)
Value:
0.48 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
Value:
2.37 mg/m³
AF for dose response relationship:
1
Justification:
NOAEL (mg/cm2)
AF for differences in duration of exposure:
1
Justification:
13 applications, each exposure: 24 h, resting period between applications: 24 h
AF for interspecies differences (allometric scaling):
1
Justification:
No AF for dermal irritation/corrosion
AF for other interspecies differences:
1
Justification:
No AF for dermal irritation/corrosion
AF for intraspecies differences:
5
Justification:
AF for workers
AF for the quality of the whole database:
1
Justification:
No additional AF required.
AF for remaining uncertainties:
1
Justification:
No additional uncertainty
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:
0.167 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
LOAEC
Value:
100 mg/m³
Modified dose descriptor starting point:
LOAEC
Value:
25 mg/m³
Explanation for the modification of the dose descriptor starting point:
LOAEC instead of a NOAEC is chosen as a dose descriptor starting point. Rationale: (1) large spacing, factor 20, between LOAEC (100 mg/m3) and NOAEC (5.3 mg/m3) (2) the nature and incidence of the observed effects at the LOAEC. Corrected LOAEC = inhalatory LOAEC * (6 h/d / 24 h/d) = inhalatory LOAEC * 0.25 = 25 mg/m3
AF for dose response relationship:
3
Justification:
LOAEC instead of NOAEC is used as dose descriptor starting point
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
no AF used for inhalation
AF for other interspecies differences:
2.5
Justification:
AF for remaining differences
AF for intraspecies differences:
10
Justification:
default AF for the general population
AF for the quality of the whole database:
1
Justification:
read-across to formulation with DBPP (Skydrol 500B-4) but this formulation is expected to me more harmful, as it contains higher TBP levels
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:
DNEL (Derived No Effect Level)
Value:
0.167 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor:
LOAEC
AF for dose response relationship:
3
Justification:
LOAEC instead of NOAEC is used as dose descriptor starting point
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
no AF used for inhalation
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
default factor for general population
AF for the quality of the whole database:
1
Justification:
read-across to formulation with DBPP (Skydrol 500B-4) but this formulation is expected to me more harmful
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 via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.69 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 440
Dose descriptor starting point:
LOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
LOAEL instead of NOAEL is used as starting dose descriptor due to the tenfold difference between the NOAEL (100 mg/kg bw) and LOAEL (1000 mg/kg bw). The only observed systemic effect at the LOAEL was a decreased choline esterase activity.
AF for dose response relationship:
3
Justification:
default AF for LOAEL
AF for differences in duration of exposure:
8
Justification:
21-day study (15 days of treatment); AF for subacute * 28/21 = 8
AF for interspecies differences (allometric scaling):
2.4
Justification:
AF for allometric scaling from rabbit
AF for other interspecies differences:
2.5
Justification:
AF for remaining differences
AF for intraspecies differences:
10
Justification:
AF for general population
AF for the quality of the whole database:
1
Justification:
No additional AF required.
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:
DNEL (Derived No Effect Level)
Value:
0.24 mg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
Value:
2.27 mg/m³
AF for dose response relationship:
1
Justification:
NOAEL (mg/m2)
AF for differences in duration of exposure:
1
Justification:
13 applications, each exposure: 24h, resting period between applications: 24h
AF for interspecies differences (allometric scaling):
1
Justification:
No AF for dermal irritation/corrosion
AF for other interspecies differences:
1
Justification:
No AF for dermal irritation/corrosion
AF for intraspecies differences:
10
Justification:
AF for general population
AF for the quality of the whole database:
1
Justification:
No AF required
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
0.025 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:
5 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
5 mg/kg bw/day
AF for dose response relationship:
1
Justification:
NOAEL is used as dose descriptor starting point
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
AF for allometric scaling from rat
AF for other interspecies differences:
2.5
Justification:
AF for remaining differences
AF for intraspecies differences:
10
Justification:
AF for general population
AF for the quality of the whole database:
1
Justification:
No AF required
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