Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.1 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
DNEL value:
159 mg/m³
Explanation for the modification of the dose descriptor starting point:
No dose descriptor is available for inhalation. It is therefore necessary to convert the available rat oral NOAEL (28-d study) into a correct starting point to obtain a DNEL for the relevant exposure pattern (worker, 8h/d, inhalation). In the absence of data, it is assumed that 50% absorption occurs by oral route. To secure a conservative NOAEL a maximum absorption (i.e. 100%) is assumed for the inhalation route. The rat Standard Respiratory Volume (SRV) for 8 h exposure is used to convert the oral NOAEL into an inhalatory NOAEL (sRVrat: 0.38 m3/kg bw/8h). An additional correction is added to take into account the worker's light activity in comparison with standard conditions (sRVhuman: 6.7 m3 for 8h exposure - worker with light activity, wRV: 10 m3 for 8h exposure). The corrected starting point is thus calculated as follows: corrected inhalatory NOAEC = oral NOAEL x (1/sRVrat) x (absorption oral rat/absorption inhalation human) x (sRVhuman/wRV); thus corrected inhalatory NOAEC for workers = 180.2 mg/kg bw/d x 0.5 x (1/0.38 m3/kg bw/8h) x (6.7 m3 for 8h exposure /10 m3 for 8h exposure) = 159 mg/m3.
AF for dose response relationship:
1
Justification:
Starting point is a NOAEC
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for oral to inhalation extrapolation
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 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):
300
Modified dose descriptor starting point:
NOAEL
DNEL value:
180.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No dose descriptor is available for dermal route. However, no additional factor is needed when performing oral to dermal extrapolation
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling from rat to human
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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:
78 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
45
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
EC3 is considered as a NOAEL
AF for differences in duration of exposure:
3
Justification:
Repeated (long term) exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Not relevant for local effects
AF for other interspecies differences:
1
Justification:
EC3 is considered as a NOAEL for humans
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for remaining uncertainties:
3
Justification:
Dermal integrity and exposure conditions (matrix effects)
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 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
DNEL value:
78 mg/m³
Explanation for the modification of the dose descriptor starting point:
No dose descriptor is available for inhalation. It is therefore necessary to convert the available rat oral NOAEL (28-d study) into a correct starting point to obtain a DNEL for the relevant exposure pattern (general exposure, 24h exposure, inhalation). In the absence of data, it is assumed that 50% absorption occurs by oral route. To secure a conservative NOAEL a maximum absorption (i.e. 100%) is assumed for the inhalation route. The rat Standard Respiratory Volume (SRV) for 24 h exposure is used to convert the oral NOAEL into an inhalatory NOAEL (sRVrat: 1.15 m3/kg bw/24h). The corrected starting point is thus calculated as follows: corrected inhalatory NOAEC = oral NOAEL x (1/sRVrat) x (absorption oral rat/absorption inhalation human); thus corrected inhalation NOAEL for general population = 180.2 mg/kg bw/d x 0.5 x (1/1.15 m3/kg bw/d) = 78 mg/m3
AF for dose response relationship:
1
Justification:
Starting point is a NOAEC
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
AF not used for oral to inhalation route extrapolation
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 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):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
180.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No dose descriptor is available for dermal route. However, no additional factor is needed when performing oral to dermal extrapolation
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling from rat to human
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 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):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
180.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation needed
AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling from rat to human
AF for other interspecies differences:
2.5
Justification:
Toxicodynamic and toxicokinetic remaining differencies
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate database
AF for remaining uncertainties:
1
Justification:
None
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population