Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
3.3 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
245 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation is needed from the oral to the inhalation route.
The NOAEL rat is converted to NOAEL human by dividing with the allometric scaling factor 4 for interspecies differences. By multiplying the NOAEL human with the default human body weight (70 kg) and dividing the default human breathing volume referring to workers (10 m3 in 8 h and light activity), this dose is then translated into an air concentration. The absorption rate for human via inhalation is not known for the substance.
NOAEL oral = 200 mg/kg b.w.
Standard human body weight = 70 kg.
Default human breathing volume for workers in 8 hours (light activity) = 10 m3.


Due to the difference between human (workers) and experimental exposure conditions, a correction factor of 1.4 is applied. Furthermore, a correction factor of 0.5 is used due to differences between absorption via oral and inhalation route.


Resulting NOAEC Inhalation = (200/4)* (70/10)* (1.4*0.5) = 245 mg/m3.

AF for dose response relationship:
1
Justification:
The starting point of the DNEL derivation is a NOAEL; default factor is 1.
AF for differences in duration of exposure:
6
Justification:
Extrapolation needed from subacute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scalling is already taken into consideration during the route-to-route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences).
AF for intraspecies differences:
5
Justification:
Default factor for workers is applied.
AF for the quality of the whole database:
1
Justification:
Good/standard quality of database.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.93 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
280 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term exposure data are available for the dermal route for the substance. Therefore, the NOAEL obtained from a subacute study on rats where the substance was administered via the oral route is used. No route-to-route extrapolation is needed as it is assumed that dermal absorption will not be higher than oral absorption; default factor is 1.
Due to the difference between human (workers) and experimental exposure conditions, a correction factor of 1.4 is applied.
The modified NOAEL is 200 mg/kg bw/day * 1.4 = 280 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
The starting point of the DNEL derivation is a NOAEL; default factor is 1.
AF for differences in duration of exposure:
6
Justification:
Extrapolation needed from subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Extrapolation from rats to humans.
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences).
AF for intraspecies differences:
5
Justification:
Default factor for workers is applied.
AF for the quality of the whole database:
1
Justification:
Good quality of database.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainities.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
medium 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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.59 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
87.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

No long-term exposure data are available for the substance via the inhalation route. Therefore, the NOAEL obtained from a subacute toxicity study on rats via the oral route was used and route-to-route extrapolation is needed.


The NOAEL rat is divided by the allometric scaling factor 4 for interspecies differences, thus obtaining the NOAEL human. The NOAEL human is then multiplied by the default human body weight (70 kg) and divided by the default human breathing volume for general population (20 m3 in 24 hours and basal caloric demand). The absorption rate for human via inhalation is not known for the substance and a correction factor of 0.5 is used due to differences in bioavailability.


 


NOAEL oral = 200 mg/kg bw/day
Standard human body weight = 70 kg
Default human breathing volume for general pobulation in 24 hours = 20 m3
Allometric scalling factor for rats as compared to humans = 4
Correction factor for differences in bioavalilability = 0.5


 


NOAEC Inhalation = (200/4)* (70/20)* 0.5 = 87.5 mg/m3.

AF for dose response relationship:
1
Justification:
The starting point for the DNEL is a NOAEL, default factor is 1.
AF for differences in duration of exposure:
6
Justification:
Extrapolation needed from subacute to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is already taken into consideration during the route-to-route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences).
AF for intraspecies differences:
10
Justification:
Default factor for general population is applied.
AF for the quality of the whole database:
1
Justification:
Good/standard quality of database.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term exposure data is available for the dermal route therefore the NOAEL resulted from a 90 days animal study is used.
No route-to-route extrapolation needed. It is assumed that dermal absorption will not be higher than oral absorption; default factor is 1.

AF for dose response relationship:
1
Justification:
The starting point of the DNEL derivation is a NOAEL; default factor is 1.
AF for differences in duration of exposure:
6
Justification:
Extrapolation needed from subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Extrapolation from rats to humans.
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences).
AF for intraspecies differences:
10
Justification:
Default factor for general population is applied.
AF for the quality of the whole database:
1
Justification:
Good/standard quality of database.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL resulted from a 90 days animal study.


 

AF for dose response relationship:
1
Justification:
The starting point of the DNEL derivation is a NOAEL; default factor is 1.
AF for differences in duration of exposure:
6
Justification:
Extrapolation needed from subacute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling from rat to humans.
AF for other interspecies differences:
2.5
Justification:
Default factor of 2.5 is applied for other interspecies differences (toxicokinetic differences not related to metabolic rate and toxicodynamic differences).
AF for intraspecies differences:
10
Justification:
Default factor for general population is applied.
AF for the quality of the whole database:
1
Justification:
Good/standard quality of database.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population