Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.47 µg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor:
LOAEC
DNEL value:
0.71 mg/m³
AF for dose response relationship:
3
Justification:
In the 90-day repeat dose inhalation toxicity study the NOAEL was 0.0586μg/L and the LOAEL was 0.710μg/L. The spacing between dose levels is wide (the difference in dose levels is more than 12-fold) and the adverse effects seen at the 0.710μg/L level were only slight and were only seen in a limited number of animals. The effects eseen at a higher dose level (2.56μg/L was the highest concentration used) indicates a steep dose-response curve and therefore it is considered that the NOAEL of 0.0586μg/L would be an extremely conservative starting point. On this basis it is considered appropriate to use the LOAEL (with an assessment factor of 3 as indicated in REACH Guidance on Information Requirements and Chemical Safety Assessment Chapter R8) in the calculation of the DNEL.
AF for differences in duration of exposure:
2
Justification:
Default Assessment Factor for extrapolation from sub-chronic (90-day) exposure to chronic axposure as indicated in Guidance on IR and CSA chapter R8.
AF for interspecies differences (allometric scaling):
1
Justification:
The adverse effects seen in the 90-day inhalation study were consistent with a local effect (irritation / corrosion) at the point of entry into the respiratory tract. The interspecies allometric scaling factor is therefore not required. It is considered that there will be a local threshold concentration above which adverse effects could be induced in the respiratory epithelium of the lung.
AF for other interspecies differences:
2.5
Justification:
Default Assessment Factor for extrapolation from rats to humans as indicated in Guidance on IR and CSA chapter R8.
AF for intraspecies differences:
5
Justification:
Default Assessment Factor for workers as indicated in Guidance on IR and CSA chapter R8.
AF for the quality of the whole database:
1
Justification:
The DNEL is calculated on the basis of a study (90-day repeat inhaled dose toxicity) which is considered reliable (study conducted according to relevant OECD test guidelines and in compliance with GLP). A further study (28-day repeat oral dose toxicity) indicated results broadly consistent with those observed in the inhalation study. On this basis the database is considered to be of satisfactory quality and adjustment of the overall assessment factor is justified.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL extrapolated from long term DNEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 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):
300
Dose descriptor starting point:
NOAEL
DNEL value:
60 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite. Correction dermal NOAEL: 60 mg/kg bw/day x 50/100a = 30 mg/kg bw/day (a % oral/dermal absorption)

AF for dose response relationship:
1
Justification:
Value is NOAEL (default assessment factor)
AF for differences in duration of exposure:
6
Justification:
Default Assessment Factor for extrapolation from sub-acute (28-day) exposure to chronic exposure as indicated in Guidance on IR and CSA chapter R8.
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human (Default Assessment Factor as indicated in Guidance on IR and CSA chapter R8).
AF for other interspecies differences:
2.5
Justification:
Default Assessment Factor for extrapolation from rats to humans as indicated in Guidance on IR and CSA chapter R8.
AF for intraspecies differences:
5
Justification:
Default Assessment Factor for workers as indicated in Guidance on IR and CSA chapter R8.
AF for the quality of the whole database:
1
Justification:
The DNEL is calculated on the basis of a study (28-day repeated dose toxicity study) which is considered reliable (study conducted according to relevant OECD test guidelines and in compliance with GLP). This study is considered to be of satisfactory quality and adjustment of the overall assessment factor is justified.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25.2 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
other: LD0
DNEL value:
1 260 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Value is LD0
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human (Default Assessment Factor as indicated in Guidance on IR and CSA chapter R8).
AF for other interspecies differences:
2.5
Justification:
Default Assessment Factor for extrapolation from rats to humans as indicated in Guidance on IR and CSA chapter R8.
AF for intraspecies differences:
5
Justification:
Default Assessment Factor for workers as indicated in Guidance on IR and CSA chapter R8.
AF for the quality of the whole database:
1
Justification:
Reliable study
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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