Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
24.86 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):
50
Dose descriptor starting point:
NOAEL
Value:
1 409.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 242.8 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
2
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
49.71 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
Dose descriptor starting point:
NOAEL
Value:
1 409.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 242.76 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-Across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
62.14 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Dose descriptor:
NOAEC
Value:
1 242.76 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
2
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
124.28 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEC
Value:
1 242.76 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.05 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:
1 409.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 409.7 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
2
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.1 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
Dose descriptor starting point:
NOAEL
Value:
1 409.76 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 409.7 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.62 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
80
Dose descriptor:
NOAEC
Value:
1 242.76 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
2
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.24 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEC
Value:
1 242.76 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
5
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Worker-Inhalation-Long-term-Systemic

NOEC calculated as described in guidance R.8 example B.3 assuming 50% and 100% absorption via oral and inhalatory routes respectively. The above factors were used to calculate a DNEL of 24.9 mg/m3

Worker-Inhalation-Acute-Systemic

The material is not classified for acute systemic effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

Worker-Inhalation-Long-term-Local

No DNEL has been derived for long-term inhalation local effects as no long-term inhalation study has been conducted. In case significant repeated exposure via the inhalation route did occur, it is anticipated that local effects would be more prominent then any possible systemic effects based on the irritant properties of the substance, i. e. irritation of the respiratory tract would be a likely local effect.

Worker-Inhalation-Acute-Local

No short term inhalatory study is available hence no DNEL has been derived. The substance is classified as a skin irritant (Category 2) based on the results of an in-vivo skin irritation study, which showed effects for erythema and edema. An acute dermal toxicity study also showed evidence of dermal irritation. However, the skin irritation study does not provide suitable dose-response information to derive a DNEL for local effects (study only exposed animals to undiluted, neat test substance). Dermal effects will be characterised by local tissue damage and irritation. In case significant exposure via the inhalation route did occur, it is anticipated that local effects would be more prominent then any possible systemic effects based on the irritant properties of the substance, i. e. irritation of the respiratory tract would be a likely local effect.

Worker-Dermal-Long-term-Systemic

NOEC calculated as described in guidance R.8 example B.5 assuming 50% and 50% absorption via oral and dermal routes respectively. The above factors were used to calculate a DNEL of 7.0 mg/m3

Worker-Dermal-Long-term-Systemic

The material is not classified for acute systemic effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

Worker-Dermal-Acute-Systemic

The test material was found to be non-sensitising in a Human Repeat Insult Patch Test (HRIPT), with this data in mind, no long term local effects are expected. The substance is a skin irritant therefore effects following repeated dermal exposure will be characterised by local irritant effects that are related to duration, quantity and concentration of the substance.

Worker-Dermal-Long-term-Local

The substance is classified as a skin irritant (Category 2) based on the results of an in-vivo skin irritation study, which showed effects for erythema and edema. An acute dermal toxicity study also showed evidence of dermal irritation. However, the skin irritation study does not provide suitable dose-response information to derive a DNEL for local effects (study only exposed animals to undiluted, neat test substance). Dermal effects will be characterised by local tissue damage and irritation.

Worker-Dermal-Acute-Local

NOEC calculated as described in guidance R.8 example B.3 assuming 50% and 100% absorption via oral and inhalatory routes respectively. The above factors were used to calculate a DNEL of 6.1 mg/m3The material is not classified for acute systemic effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

Worker-Hazard for eyes

Classified as eye irritant (Category 2)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.13 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):
100
Dose descriptor starting point:
NOAEL
Value:
1 409.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
612.91 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
2
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12.26 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):
50
Dose descriptor starting point:
NOAEL
Value:
1 409.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
612.91 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.32 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Dose descriptor:
NOAEC
Value:
612.91 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
2
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30.65 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Dose descriptor starting point:
NOAEC
Value:
612.91 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
1
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.52 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):
400
Dose descriptor starting point:
NOAEL
Value:
1 409.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 409.7 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
2
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.05 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:
1 409.7 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.81 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
160
Dose descriptor:
NOAEC
Value:
612.91 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
2
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.62 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
80
Dose descriptor starting point:
NOAEC
Value:
612.91 mg/m³
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
1
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.52 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):
400
Dose descriptor starting point:
NOAEL
Value:
1 409.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for differences in duration of exposure:
2
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.05 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:
1 409.7 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default ECHA assessment
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA assessment
AF for other interspecies differences:
2.5
Justification:
Default ECHA assessment
AF for intraspecies differences:
10
Justification:
Default ECHA assessment
AF for the quality of the whole database:
2
Justification:
Read-across
AF for remaining uncertainties:
1
Justification:
Default ECHA assessment

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

General population-Inhalation-Long-term-Systemic

NOEC calculated as described in guidance R.8 example B.3 assuming 50% and 100% absorption via oral and inhalatory routes respectively. The above factors were used to calculate a DNEL of 6.1 mg/m3

General population-Inhalation-Acute-Systemic

The material is not classified for acute systemic effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

General population-Inhalation-Long-term-Local

No DNEL has been derived for long-term inhalation local effects as no long-term inhalation study has been conducted. In case significant repeated exposure via the inhalation route did occur, it is anticipated that local effects would be more prominent then any possible systemic effects based on the irritant properties of the substance, i. e. irritation of the respiratory tract would be a likely local effect.

General population-Inhalation-Acute-Local

No short term inhalatory study is available hence no DNEL has been derived. The substance is classified as a skin irritant (Category 2) based on the results of an in-vivo skin irritation study, which showed effects for erythema and edema. An acute dermal toxicity study also showed evidence of dermal irritation. However, the skin irritation study does not provide suitable dose-response information to derive a DNEL for local effects (study only exposed animals to undiluted, neat test substance). Dermal effects will be characterised by local tissue damage and irritation. In case significant exposure via the inhalation route did occur, it is anticipated that local effects would be more prominent then any possible systemic effects based on the irritant properties of the substance, i. e. irritation of the respiratory tract would be a likely local effect.

General population-Dermal-Long-term-Systemic

NOEC calculated as described in guidance R.8 example B.5 assuming 50% and 50% absorption via oral and dermal routes respectively. The above factors were used to calculate a DNEL of 3.5 mg/m3

General population-Dermal-Long-term-Systemic

The material is not classified for acute systemic effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

General population-Dermal-Acute-Systemic

The test material was found to be non-sensitising in a Human Repeat Insult Patch Test (HRIPT), with this data in mind, no long term local effects are expected. The substance is a skin irritant therefore effects following repeated dermal exposure will be characterised by local irritant effects that are related to duration, quantity and concentration of the substance.

General population-Dermal-Long-term-Local

The substance is classified as a skin irritant (Category 2) based on the results of an in-vivo skin irritation study, which showed effects for erythema and edema. An acute dermal toxicity study also showed evidence of dermal irritation. However, the skin irritation study does not provide suitable dose-response information to derive a DNEL for local effects (study only exposed animals to undiluted, neat test substance). Dermal effects will be characterised by local tissue damage and irritation.

General population-Dermal-Acute-Local

NOEC calculated as described in guidance R.8 example B.3 assuming 50% and 100% absorption via oral and inhalatory routes respectively. The above factors were used to calculate a DNEL of 6.1 mg/m3The material is not classified for acute systemic effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

General population-Oral-Long-term-Systemic

NOEL provided by 90d read across study. The above factors were used to calculate a DNEL of 3.5 mg/m3

General population-Oral-Acute-Systemic

The material is not classified for acute systemic effects, therefore derivation of acute DNEL is not required. Long term DNELs are considered sufficient to ensure acute effects do not occur.

General population-Hazard for eyes

Classified as eye irritant (Category 2)