Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.44 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
Modified dose descriptor starting point:
NOAEC
Value:
22 mg/m³
Explanation for the modification of the dose descriptor starting point:
R.8 Example B. 3 Modification of the starting point
AF for dose response relationship:
1
Justification:
NOAEC
AF for differences in duration of exposure:
2
Justification:
subchronic-chronic
AF for interspecies differences (allometric scaling):
1
Justification:
route-route concentration correction
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
worker default
AF for the quality of the whole database:
2
Justification:
read across
AF for remaining uncertainties:
1
Justification:
none known
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:
1.25 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
Modified dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
R.8 Example B. 5 Dermal exposure; oral N(L)OAEL rat
AF for dose response relationship:
1
Justification:
NOAEL
AF for differences in duration of exposure:
2
Justification:
Subchronic - Chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat default
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
worker default
AF for the quality of the whole database:
2
Justification:
data on substance
AF for remaining uncertainties:
1
Justification:
none known
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:
0.72 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 500
Dose descriptor:
other: LOAEL
AF for dose response relationship:
3
Justification:
LOAEL from LLNA EC3
AF for differences in duration of exposure:
10
Justification:
specific R.8 page 125
AF for interspecies differences (allometric scaling):
10
Justification:
specific R.8 page 125
AF for other interspecies differences:
1
Justification:
accounted for above
AF for intraspecies differences:
5
Justification:
worker default
AF for the quality of the whole database:
1
Justification:
data available on substance
AF for remaining uncertainties:
1
Justification:
specific: matrix effect R.8 page 125
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Worker-Inhalation-Long-term-Systemic

NOAEC 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 0.44 mg/m3

Worker-Inhalation-Acute-Systemic

The material is not classified for acute 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 skin irritation studies. 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

NOAEL calculated as described in guidance R.8 example B.5 assuming 50% and 5% absorption via oral and dermal routes respectively. The above factors were used to calculate a DNEL of 1.25 mg/m3

Worker-Dermal-Acute-Systemic

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

Worker-Dermal-Long-term-Local

LLNA shows an EC3 of  4.3 %, according to Guidance R.8-10 this can be used to calculate a corrected LOAEL for the purposes of calculating a DNEL, provided specific assessment factors are used as above.

Worker-Dermal-Acute-Local

The substance is classified as a skin irritant (Category 2) based on the results of skin irritation studies. 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-Hazard for eyes

Substance has not been classified has irritating to the eye following results of an in-vitro and an in-vivo study, as such no specific hazard identified.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.11 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):
100
Modified dose descriptor starting point:
NOAEC
Value:
11 mg/m³
Explanation for the modification of the dose descriptor starting point:
R.8 Example B. 3 Modification of the starting point
AF for dose response relationship:
1
Justification:
NOAEC
AF for differences in duration of exposure:
2
Justification:
subchronic-chrnic
AF for interspecies differences (allometric scaling):
1
Justification:
route-route concentration correction
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
general population - default
AF for the quality of the whole database:
2
Justification:
read across
AF for remaining uncertainties:
1
Justification:
none known
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:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.625 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):
400
Modified dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
R.8 Example B. 5 Dermal exposure; oral N(L)OAEL rat
AF for dose response relationship:
1
Justification:
NOEL
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat default
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
general population default
AF for the quality of the whole database:
2
Justification:
read across
AF for remaining uncertainties:
1
Justification:
none known
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:
0.36 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
3 000
Dose descriptor:
other: LOAEL
AF for dose response relationship:
3
Justification:
LOAEL
AF for differences in duration of exposure:
10
Justification:
specific R.8 page 125
AF for interspecies differences (allometric scaling):
10
Justification:
specific R.8 page 125
AF for other interspecies differences:
1
Justification:
accounted for above
AF for intraspecies differences:
10
Justification:
general population default
AF for the quality of the whole database:
1
Justification:
data on substance
AF for remaining uncertainties:
1
Justification:
specific: matrix effect R.8 page 125
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
62.5 µg/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):
400
Modified dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No starting point modification required
AF for dose response relationship:
1
Justification:
NOEL
AF for differences in duration of exposure:
2
Justification:
subchronic - chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat default
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
general population default
AF for the quality of the whole database:
2
Justification:
read across
AF for remaining uncertainties:
1
Justification:
none known
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

General population-Inhalation-Long-term-Systemic

NOAEC 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 0.11 mg/m3

General population-Inhalation-Acute-Systemic

The material is not classified for acute 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 skin irritation studies. 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

NOAEL calculated as described in guidance R.8 example B.5 assuming 50% and 5% absorption via oral and dermal routes respectively. The above factors were used to calculate a DNEL of 0.625 mg/m3

General population-Dermal-Acute-Systemic

The material is not classified for acute 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-Long-term-Local

LLNA shows an EC3 of 4.3 %, according to Guidance R.8-10 this can be used to calculate a corrected LOAEL for the purposes of calculating a DNEL, provided specific assessment factors are used as above.

General population-Dermal-Acute-Local

The substance is classified as a skin irritant (Category 2) based on the results of skin irritation studies. 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-Oral-Long-term-Systemic

NOAEL provided by 90d read across study. The above factors were used to calculate a DNEL of 62.5 µg/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

Substance has not been classified has irritating to the eye following results of an in-vitro and an in-vivo study, as such no specific hazard identified.