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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
35 µg/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):
25
Dose descriptor starting point:
NOAEL
Value:
1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
0.88 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL derivation was done according to the ECHA guidance R.8 using the rat oral 90-day NOAEL as starting point and route-to-route extrapolation.


Corrected inhalatory NOAEC = Oral NOAEL x 1 / sRVrat x Abs (oral, rat) / Abs (inhal, human) x sRVhuman / wRV


 


In the absence of substance-specific information the default values were used for the route-to-route extrapolation, i.e. 100% absorption by inhalation and 50% by oral route according to the R.8 Guidance document.

AF for dose response relationship:
1
Justification:
No dose-response relationship issue identified
AF for differences in duration of exposure:
2
Justification:
Default value for subchronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Route-to route-extrapolation performed
AF for other interspecies differences:
2.5
Justification:
Default value for other TK differences
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Database of appropriate quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainty 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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 µg/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):
100
Dose descriptor starting point:
NOAEL
Value:
1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the absence of specific study by the dermal route, the DNEL for long-term systemic effects by the dermal route was derived using the rat oral 90-day NOAEL as a starting point.
Dermal NOAEL = Oral NOAEL x Abs (oral, rat) / Abs (dermal, human)

For the route-to route-extrapolation, in the absence of substance-specific data, in a worst-case approach, both oral absorption in rats and dermal absorption in humans were considered to be 100%.

AF for dose response relationship:
1
Justification:
No dose-response relationship issue identified
AF for differences in duration of exposure:
2
Justification:
Default value for subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rats
AF for other interspecies differences:
2.5
Justification:
Default value for other TK differences
AF for intraspecies differences:
5
Justification:
Default value for workers
AF for the quality of the whole database:
1
Justification:
Database of appropriate quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainty identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Two DNEL values for industrial workers were derived for systemic effects after long-term exposure: a dermal DNEL and an inhalation DNEL. Both values were based on the rat NOAEL determined in the 90-day repeated toxicity study: 1 mg/kg bw/day. As this NOAEL was observed in an oral study, a route-to-route extrapolation was needed in order to obtain the correct starting points for the derivation of the DNEL. The correct starting points were than divided by an overall assessment factor, which was a result of various consideration on uncertainties in inter-and intra-species variations, and on differences in the duration of exposure between test animals and humans. Moreover also the whole quality of the database was considered.


 


For acute dermal local effects, no DNEL could be derived, as the key study used to evaluate this endpoint was an in vitro study which provided only qualitative data. The acute dermal toxicity study was used, in this case, as supporting the evidence of the irritation potential of the substance.


 


For acute dermal systemic effects, the derivation of a DNEL was not considered appropriate because no specific systemic hazard has been identified for acute dermal exposure and no peak exposure is expected to occur.


 


Moreover the DNELs derived for the long-term exposure are considered conservative enough to protect also from acute exposure effects.


Local effects after repeated dermal exposure were evaluated from a qualitative point of view, considering the irritation potential of the substance and the negative results of the sensitization tests.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9 µg/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
Dose descriptor starting point:
NOAEL
Value:
1 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
0.435 mg/m³
Explanation for the modification of the dose descriptor starting point:
Corrected inhalatory NOAEC = Oral NOAEL x 1 / sRVrat x Abs (oral, rat) / Abs (inhal, human)
AF for dose response relationship:
1
Justification:
No dose-response relationship issue identified
AF for differences in duration of exposure:
2
Justification:
Default value for subchronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Route-to route-extrapolation performed
AF for other interspecies differences:
2.5
Justification:
Default value for other TK differences
AF for intraspecies differences:
10
Justification:
Default value for general population
AF for the quality of the whole database:
1
Justification:
Database of appropriate quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainty 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:
DNEL (Derived No Effect Level)
Value:
5 µg/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):
200
Dose descriptor starting point:
NOAEL
Value:
1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the absence of specific study by the dermal route, the DNEL for long-term systemic effects by the dermal route was derived using the rat oral 90-day NOAEL as a starting point and route-to-route extrapolation. The DNEL derivation was done according to the ECHA guidance R.8.
Dermal NOAEL = Oral NOAEL x Abs (oral, rat) / Abs (dermal, human)

For the route-to route-extrapolation, in the absence of substance-specific data, in a worst-case approach, both oral absorption in rats and dermal absorption in humans were considered to be 100%. No modification of the dose descriptor starting point is necessary.

AF for dose response relationship:
1
Justification:
No dose-response relationship issue identified
AF for differences in duration of exposure:
2
Justification:
Default value for subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Default value for rats
AF for other interspecies differences:
2.5
Justification:
Default value for other TK differences
AF for intraspecies differences:
10
Justification:
Default value for the general population
AF for the quality of the whole database:
1
Justification:
Database of appropriate quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainty identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 µg/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):
1 000
Dose descriptor starting point:
NOAEL
Value:
1 mg/kg bw/day
AF for dose response relationship:
1
Justification:
(Default)
AF for differences in duration of exposure:
2
Justification:
Default value for subchronic study (NOAEL from a 90-day study)
AF for interspecies differences (allometric scaling):
4
Justification:
(Default)
AF for other interspecies differences:
2.5
Justification:
(Default)
AF for intraspecies differences:
10
Justification:
(Default)
AF for the quality of the whole database:
1
Justification:
Default value. Information in addition to standard requirements was available in the dataset.
AF for remaining uncertainties:
5
Justification:
An additional assessment factor of 5 was used to account for additional uncertainties for the general population.
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

Although not required at this tonnage band, the DNEL for long-term systemic effects via inhalation and oral routes were derived for the general population to assess potential risk for human via the environment.  For inhalation, a route-to-route extrapolation was applied to the oral rat NOAEL of 1 mg/kg bw/day identified in the 90-day repeated toxicity study, and using assessment factors recommended in ECHA Guidance R.8.