Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
118 µg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
225
Modified dose descriptor starting point:
LOAEC
Value:
26.45 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic inhalative effects was estimated via route-to-route-extrapolation and assessment factors were applied, all according to ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health and ECHA: How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14. Details are given in the discussion.
AF for dose response relationship:
3
Justification:
Starting point is a LOAEL/LOAEC
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic. DNEL is based on a (oral) OECD 422 (28 d) (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
Worker
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.05 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):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
88.16 mg/m³
Explanation for the modification of the dose descriptor starting point:
The acute inhalation DNEL were calculated froma derived, via route-to route extrapolation, from a estimated NOAEL from a repeated dose study (OECD 422), in accordance with ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health and ECHA How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14. Details are given in the discussion.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL/NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
Worker
AF for the quality of the whole database:
1

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33.33 µg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
900
Modified dose descriptor starting point:
LOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic dermal effects was estimated via route-to-route-extrapolation and assessment factors were applied, all according to ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health and ECHA: How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14. Details are given in the discussion.
AF for dose response relationship:
3
Justification:
Starting point is a LOAEL/LOAEC
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic. DNEL is based on a (oral) OECD 422 (28 d) (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
Worker
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 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):
50
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The acute dermal DNEL were calculated froma derived, via route-to route extrapolation, from a estimated NOAEL from a repeated dose study (OECD 422), in accordance with ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health and ECHA How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14. Details are given in the discussion.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL/NOAEC
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
Worker
AF for the quality of the whole database:
1

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Following Absorpsion Oral=0.5 Absorption Inhalation=Absorption dermal. 28 days study is subacute, hence AF=6 in extrapolation to long term.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
29.99 µg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
450
Modified dose descriptor starting point:
LOAEC
Value:
13.04 mg/m³
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic inhalative effects was estimated via route-to-route-extrapolation and assessment factors were applied, all according to ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health and ECHA: How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14. Details are given in the discussion. The DNEL for systemic inhalative effects was estimated via route-to-route-extrapolation and assessment factors were applied, all according to ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health and ECHA: How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14. Details are given in the discussion.
AF for dose response relationship:
3
Justification:
Starting point is a LOAEL/LOAEC
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic. DNEL is based on a (oral) OECD 422 (28 d) (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Acute/short 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
43.47 mg/m³
Explanation for the modification of the dose descriptor starting point:
The acute inhalation DNEL were calculated froma derived, via route-to route extrapolation, from a estimated NOAEL from a repeated dose study (OECD 422), in accordance with ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health and ECHA How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14. Details are given in the discussion.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL/NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for inhalation route
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17 µg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 800
Modified dose descriptor starting point:
LOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The DNEL for systemic dermal effects was estimated via route-to-route-extrapolation and assessment factors were applied, all according to ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health and ECHA: How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14. Details are given in the discussion.
AF for dose response relationship:
3
Justification:
Starting point is a LOAEL/LOAEC
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic. DNEL is based on a (oral) OECD 422 (28 d) (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Acute/short 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The acute dermal DNEL were calculated froma derived, via route-to route extrapolation, from a estimated NOAEL from a repeated dose study (OECD 422), in accordance with ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health and ECHA How to prepare toxicological summaries in IUCLID and how to derive DNELs Practical Guide 14. Details are given in the discussion.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL/NOAEC
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17 µg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 800
Modified dose descriptor starting point:
LOAEL
Value:
30 µg/kg bw/day
AF for dose response relationship:
3
Justification:
Starting point is a LOAEL/LOAEC
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic. DNEL is based on a (oral) OECD 422 (28 d) (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
100 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
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL/NOAEC
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Please refer to the discussion on DNELs for workers mentioned above.