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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
16.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 234 mg/m³
Explanation for the modification of the dose descriptor starting point:

The default ECHA approach was used to modify the dose descriptor starting point:


- To convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38 m3/kg bw/8 h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8-h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8-h exposure period).


- The difference in exposure duration (7 days/week for rats, 5 days/week for worker) is taken into account in the calculation. 


- Regarding absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e. 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested in the ECHA Guidance Document, Chapter R.8 (Version 2.1, November 2012).


Thus, the corrected dose descriptor for inhalation route is 1000 x (1/ 0.38) x (6.7 / 10) x (7 / 5) x (1/2) = 1234 mg/m3 for workers.

Justification:
Default (DNEL calculator) - the dose descriptor starting point is a NOAEL
Justification:
Default (DNEL calculator) - subacute study
Justification:
Default (DNEL calculator) - not required as the differences in allometry were taken into account in the conversion of oral to inhalation starting point
Justification:
Default (DNEL calculator) - remaining toxicokinetic and toxicodynamic differences
Justification:
Default (DNEL calculator) - workers
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to OECD Guidelines and are GLP-compliant
Justification:
No remaining uncertainties 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:
4.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The default ECHA approach was used to modify the dose descriptor starting point:


- For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. It is considered that dermal absorption will not be higher than oral absorption, therefore no default factors were introduced when peforming oral to dermal extrapolation of starting dose.


- Difference in exposure duration (7 days/week for rats, 5 days/week for worker) is taken into account in the calculation.


Thus, the corrected dose descriptor for dermal route is 1000 x 7 / 5 = 1400 mg/ kg bw/day

Justification:
Default (DNEL calculator) - the dose descriptor starting point is a NOAEL
Justification:
Default (DNEL calculator) - subacute study
Justification:
Default (DNEL calculator) - rat
Justification:
Default (DNEL calculator) - allometric scaling (rats)
Justification:
Default (DNEL calculator) - remaining toxicokinetic and toxicodynamic differences
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to OECD Guidelines and are GLP-compliant
Justification:
No remaining uncertainties 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

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:
DNEL (Derived No Effect Level)
Value:
2.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
435 mg/m³
Explanation for the modification of the dose descriptor starting point:

The default ECHA approach was used to modify the dose descriptor starting point:


- To convert the oral NOAEL into inhalatory NOAEC, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 1.15 m3/kg bw/24 h).


- Regarding absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e. 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested in the ECHA Guidance Document, Chapter R.8 (Version 2.1, November 2012).


Thus, the corrected dose descriptor for inhalation route is 1000 x (1/ 1.15) x (1/2) = 435 mg/m3 for general population.

Justification:
Default (DNEL calculator) - the dose descriptor starting point is a NOAEL
Justification:
Default (DNEL calculator) - subacute study
Justification:
Default (DNEL calculator) - not required as the differences in allometry were taken into account in the conversion of oral to inhalation starting point
Justification:
Default (DNEL calculator) - remaining toxicokinetic and toxicodynamic differences
Justification:
Default (DNEL calculator) – general population
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to OECD Guidelines and are GLP-compliant
Justification:
No remaining uncertainties 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:
1.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The default ECHA approach was used to modify the dose descriptor starting point:


- For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. It is considered that dermal absorption will not be higher than oral absorption, therefore no default factors were introduced when peforming oral to dermal extrapolation of starting dose.


Thus, the dose descriptor for dermal route is 1000 mg/ kg bw/day.

Justification:
Default (DNEL calculator) - the dose descriptor starting point is a NOAEL
Justification:
Default (DNEL calculator) - subacute study
Justification:
Default (DNEL calculator) – rat
Justification:
Default (DNEL calculator) - remaining toxicokinetic and toxicodynamic differences
Justification:
Default (DNEL calculator) – general population
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to OECD Guidelines and are GLP-compliant.
Justification:
No remaining uncertainties 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:
DNEL (Derived No Effect Level)
Value:
1.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Justification:
Default (DNEL calculator) - the dose descriptor starting point is a NOAEL
Justification:
Default (DNEL calculator) - subacute study
Justification:
Default (DNEL calculator) – rat
Justification:
Default (DNEL calculator) - remaining toxicokinetic and toxicodynamic differences
Justification:
Default (DNEL calculator) – general population
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to OECD Guidelines and are GLP-compliant
Justification:
No remaining uncertainties 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

No hazard for the eyes has been identified in the available study.