Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:
based on log Ko/w and on water solubility, it is assumed that the substance is not completely absorbed by inhalation exposure and that inhalation absorption factor doesn’t exceed oral absorption factor. Therefore ABS oral rat and ABS inh human are assumed to be equivalent.
AF for dose response relationship:
1
Justification:
default factor
AF for differences in duration of exposure:
4
Justification:
as the exposure in rats was at least 44 days, a factor of 4 for subacute-to-chronic extrapolation is applied instead of a factor 6 when using a 28 days study
AF for interspecies differences (allometric scaling):
1
Justification:
no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed
AF for other interspecies differences:
2.5
Justification:
default factor
AF for intraspecies differences:
5
Justification:
default factor
AF for the quality of the whole database:
1
Justification:
default factor
AF for remaining uncertainties:
1
Justification:
default factor
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:
5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Correction for dermal and oral absorption rates : factor 1/10 (based on Guidance on information requirements and chemical safety assessment, Chapter R 7.12) Dermal absorption is supposed very low for several reasons.1/ The substance is dry and practically non soluble in water (<0.62 mg/l, if water solubility is < 1 mg/l, dermal uptake is likely to be low); the experimental log Kow is > 5.5 and the calculated log Kow is 7.3; therefore very few of the substance goes from the stratum corneum to the epidermidis. 2/ The molecular weight is 338.5 g/mol, so not really in favour of dermal absorption (below 100: in favour of dermal absorption, above 500, not in favour of absorption) 3/ the substance is not a skin irritant, therefore no increase of skin absorption is expected. Therefore, dermal absorption can be reasonably estimated to be lower than 10%. No data is available on absorption by oral route. It is therefore assumed that oral absorption factor is 100 %.
AF for dose response relationship:
1
Justification:
default factor
AF for differences in duration of exposure:
4
Justification:
as the exposure in rats was at least 44 days, a factor of 4 for subacute-to-chronic extrapolation is applied instead of a factor 6 when using a 28 days study
AF for interspecies differences (allometric scaling):
4
Justification:
default factor for rats
AF for other interspecies differences:
2.5
Justification:
default factor
AF for intraspecies differences:
5
Justification:
default factor
AF for the quality of the whole database:
1
Justification:
default factor
AF for remaining uncertainties:
1
Justification:
default factor
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
hazard unknown (no further information necessary)
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:
hazard unknown (no further information necessary)
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