Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.83 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
437 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeat dose inhalation data available, only NOAEL (oral).
AF for dose response relationship:
1
Justification:
NOAEC
AF for differences in duration of exposure:
6
Justification:
Standard default sub-acute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not applied as NOAEC is used.
AF for other interspecies differences:
2.5
Justification:
Standard default
AF for intraspecies differences:
5
Justification:
Standard default for workers
AF for the quality of the whole database:
1
Justification:
Data available 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:
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:
1.67 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):
180
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No repeat dose dermal data available, only NOAEL (oral).
AF for dose response relationship:
1
Justification:
NOEL
AF for differences in duration of exposure:
6
Justification:
Standard default, sub-acute to chronic
AF for interspecies differences (allometric scaling):
2.4
Justification:
Standard default rat to human
AF for other interspecies differences:
2.5
Justification:
Standard default
AF for intraspecies differences:
5
Justification:
Standard default for workers
AF for the quality of the whole database:
1
Justification:
Data available 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:
7.43 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
750
Dose descriptor:
other: LOAEL
AF for dose response relationship:
3
Justification:
LOAEL
AF for differences in duration of exposure:
10
Justification:
skin sensitisation specific guidance (R8 page 131)
AF for interspecies differences (allometric scaling):
5
Justification:
skin sensitisation specific guidance (R8 page 132), reduced from 10 to 5 due to referenced correlation to human data within study
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:
None known
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 dermal DNEL for long term exposure (systemic effects) was based on the oral 14-Day study, in which a NOAEL of 300 mg/kg/day was established. The assessment factors were:

AF differences in exposure: 6,

AF for allometric scaling: 2.4 (rabbit),

AF for other interspecies differences: 2.5,

AF for intraspecies differences: 5

 

The inhalation DNEL for long term exposure (systemic effects) was based on the oral 14-Day study, in which a NOAEL of 300 mg/kg/day was established, this was then corrected for inhalation via route to route extrapolation to give a starting point of 291 mg/m3. The assessment factors were:

AF differences in exposure: 6,

AF for allometric scaling: 1 (accounted for in route to route extrapolation),

AF for other interspecies differences: 2.5,

AF for intraspecies differences: 5

 

The dermal DNEL for long term exposure (local effects) was based on the LLNA study, in which a LOAEL of 22.3% in 25µl liquid was established to give an LOAEL of 5575µg/cm2.. The assessment factors were:

• interspecies differences; 5 (p132) (lowered from 10 due to human data correlation referred to in study)

• intraspecies differences; 5 worker (p38)

• differences in duration of exposure; 10 (p131) (factor could be reduced for general population due to level of exposure to formulated material, for worst case, 10 has been assumed)

• issues related to dose-response; 3 (p36)

• quality of whole database; 1 (p36)

• sensitisation specific matrix effect; 1 (p131) (assumed 1: “the matrix is very similar to the matrix used to determine the EC3 and is not expected to increase the potential for induction of sensitisation” otherwise 3 or 10)

 

As no acute effects were recorded and no classification and labelling is necessary, no acute DNEL is derived in accordance with the guidance. It is assumed that the long term DNEL is sufficient to ensure acute effects do not occur.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.45 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
217 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeat dose inhalation data available, only NOAEL (oral).
AF for dose response relationship:
1
Justification:
NOEL
AF for differences in duration of exposure:
6
Justification:
sub-chronic
AF for interspecies differences (allometric scaling):
1
Justification:
concentration (scaling already acounted for in corrected NOAEC)
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
Data on substance available
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.83 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):
360
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No repeat dose dermal data available, only NOAEL (oral).
AF for dose response relationship:
1
Justification:
NOEL
AF for differences in duration of exposure:
6
Justification:
sub-chronic
AF for interspecies differences (allometric scaling):
2.4
Justification:
rabbit
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
None known
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.72 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
AF for differences in duration of exposure:
10
Justification:
specific skin sensitisation guidance(R8 p131)
AF for interspecies differences (allometric scaling):
5
Justification:
specific skin sensitisation guidance 10 (R8 p132), reduced to 5 due to referenced correlation to human data within study
AF for other interspecies differences:
1
Justification:
accounted for above
AF for intraspecies differences:
10
Justification:
general popultaion default
AF for the quality of the whole database:
1
Justification:
data on substance available
AF for remaining uncertainties:
1
Justification:
None known
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:
0.83 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):
360
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no extrapolation required.
AF for dose response relationship:
1
Justification:
NOEL
AF for differences in duration of exposure:
6
Justification:
sub-chronic
AF for interspecies differences (allometric scaling):
2.4
Justification:
rabbit
AF for other interspecies differences:
2.5
Justification:
remaining differences
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
data on substance available
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

The inhalation DNEL for long term exposure (systemic effects) was based on the oral 14-Day study, in which a NOAEL of 300 mg/kg/day was established, this was then corrected for inhalation via route to route extrapolation to give a starting point of 437 mg/m3 for workers and 217mg/m3 for general population. The assessment factors were:

AF differences in exposure: 6,

AF for allometric scaling: 1 (accounted for in route to route extrapolation),

AF for other interspecies differences: 2.5,

AF for intraspecies differences: 5 workers 10 general population

The dermal DNEL for long term exposure (systemic effects) was based on the oral 14-Day study, in which a NOAEL of 300 mg/kg/day was established. The assessment factors were:

AF differences in exposure: 6,

AF for allometric scaling: 2.4 (rabbit),

AF for other interspecies differences: 2.5,

AF for intraspecies differences: 5 workers 10 general population

The oral DNEL for long term exposure (systemic effects) was based on the oral 14-Day study, in which a NOAEL of 300 mg/kg/day was established. The assessment factors were:

AF differences in exposure: 6,

AF for allometric scaling: 2.4 (rabbit),

AF for other interspecies differences: 2.5,

AF for intraspecies differences: 10

  

The dermal DNEL for long term exposure (local effects) was based on the LLNA study, in which a LOAEL of 22.3% in 25µl liquid was established to give an LOAEL of 5575µg/cm2.. The assessment factors were:

• interspecies differences; 5 (p132) (lowered from 10 due to human data correlation referred to in study)

• intraspecies differences; 5 workers 10 general population (p38)

• differences in duration of exposure; 10 (p131) (factor could be reduced for general population due to level of exposure to formulated material, for worst case, 10 has been assumed)

• issues related to dose-response; 3 (p36)

• quality of whole database; 1 (p36)

• sensitisation specific matrix effect; 1 (p131) (assumed 1: “the matrix is very similar to the matrix used to determine the EC3 and is not expected to increase the potential for induction of sensitisation”)

 

As no acute effects were recorded and no classification and labelling is necessary, no acute DNEL is derived in accordance with the guidance. It is assumed that the long term DNEL is sufficient to ensure acute effects do not occur.