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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
0.08 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
0.08 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEC determined in the sub-chronic inhalation toxicity study in rats was selected as dose descriptor to calculate the DNEL, inhalation, long-term, systemic and local. In this study, 4 mg/m3 (0.004 mg/L) was considered as the NOAEC local and systemic based on adverse effects reported in the lungs and effects on body weight reported at higher doses. According to ECHA guidance R8.4.2, Corrected NOAEC = Inhalatory NOAEC * (exp. cond. rat / exp. cond. human) = inhalatory NOAEC *((6h/d)/(8h/d))*(6.7 m3 (8h) /10m3 (8h)). Therefore corrected NOAEC = 4 * (6/8) * (6.7/10) = 0.08 mg/m3
AF for dose response relationship:
1
Justification:
NOAEL used a starting point
AF for differences in duration of exposure:
2
Justification:
Sub-chronic (OECD 413 study) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling used when setting an inhalation DNEL based on an inhalation animal study
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Standard factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Modified dose descriptor starting point:
LOAEC
Value:
861 mg/m³
Explanation for the modification of the dose descriptor starting point:
The LOAEC determined in the acute inhalation toxicity study in rats was selected as dose descriptor to calculate the DNEL, inhalation, short-term, systemic. In this study, 510 mg/m3 (0.51 mg/L) was considered as the LOAEC as it was the lowest dose at which there was no mortality but presence of clinical signs indicative of weak condition and respiratory difficulties. In order to take into account the differences in exposure duration and respiratory volume between workers and animal study conditions, the following modifications to the dose descriptor were applied: 1) Modification of the dose descriptor to consider time extrapolation (4h-exposure in rat study v.s. 15 min (i.e. 0.25h) in workers for peak exposure): According to ECHA Guidance R 8 App. 8, the modified Haber’s law should be applied (Cn x t = k where ‘C’ is the concentration, ‘t’ is the time, ‘n’ is a regression coefficient (n=3 by default for extrapolating from longer to shorter exposure durations) and ‘k’ is a constant). => Concentration corrected for time = ((510e3 * 4)/0,25)e1/3 = 1285 mg/m3. 2) Modification of the dose descriptor to consider the respiratory volume: => Concentration corrected (LOAEC corr.) for respiratory volume = 1285 * 6.7/10 = 861 mg/m3.
AF for dose response relationship:
3
Justification:
LOAEC used a starting point
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling used when setting an inhalation DNEL based on an inhalation animal study
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Standard factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor:
NOAEC
Value:
0.08 mg/m³
AF for dose response relationship:
1
Justification:
NOAEL used a starting point
AF for differences in duration of exposure:
2
Justification:
Sub-chronic (OECD 413 study) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling used when setting an inhalation DNEL based on an inhalation animal study
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Standard factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
34 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Dose descriptor starting point:
LOAEC
AF for dose response relationship:
3
Justification:
LOAEC used a starting point
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling used when setting an inhalation DNEL based on an inhalation animal study
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Standard factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.44 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
Value:
133 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In the absence of data on absorption via the dermal route, a default factor of 1 is applied as recommended by ECHA R8 guidance (dermal absorption is assumed not to be higher than oral absorption).
AF for dose response relationship:
1
Justification:
NOAEL used as starting point
AF for differences in duration of exposure:
6
Justification:
Subacute (OECD 422 study) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor for rat to human extrapolation
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
Standard factor for workers
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
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:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium 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:
0.02 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
Value:
0.02 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
0.02 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEC determined in the sub-chronic inhalation toxicity study in rats was selected as dose descriptor to calculate the DNEL, inhalation, long-term, systemic and local. In this study, 4 mg/m3 (0.004 mg/L) was considered as the NOAEC local and systemic based on adverse effects reported in the lungs and effects on body weight reported at higher doses.

According to ECHA guidance R8.4.2, Corrected NOAEC = Inhalatory NOAEC * (exp. cond. rat / exp. cond. human) = inhalatory NOAEC *(6h/d)/(24h/d). Therefore corrected NOAEC = 4 * (6/24) = 0.02 mg/m3

AF for dose response relationship:
1
Justification:
NOAEL used a starting point
AF for differences in duration of exposure:
2
Justification:
Sub-chronic (OECD 413 study) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling used when setting an inhalation DNEL based on an inhalation animal study
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Standard factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
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:
0.02 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor:
NOAEC
Value:
0.02 mg/m³
AF for dose response relationship:
1
Justification:
NOAEL used a starting point
AF for differences in duration of exposure:
2
Justification:
Sub-chronic (OECD 413 study) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling used when setting an inhalation DNEL based on an inhalation animal study
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Standard factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
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:
0.22 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
Value:
133 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In the absence of data on absorption via the dermal route, a default factor of 1 is applied as recommended by ECHA R8 guidance (dermal absorption is assumed not to be higher than oral absorption).
AF for dose response relationship:
1
Justification:
NOAEL used as starting point
AF for differences in duration of exposure:
6
Justification:
Subacute (OECD 422 study) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor for rat to human extrapolation
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Standard factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
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:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.22 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
Value:
133 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No modification of the dose descriptor is needed since it was determined in an oral toxicity study.
AF for dose response relationship:
1
Justification:
NOAEL used as starting point
AF for differences in duration of exposure:
6
Justification:
Subacute (OECD 422 study) to chronic duration extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
Standard factor for rat to human extrapolation
AF for other interspecies differences:
2.5
Justification:
Standard factor for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Standard factor for general population
AF for the quality of the whole database:
1
Justification:
Appropriate completeness and adequacy of the database
AF for remaining uncertainties:
1
Justification:
Not applicable
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population