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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.235 mg/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:
0.84 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
5.88 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a 52-week oral toxicity study in dogs (key, 1991, HLA 6111-112). To convert the dog oral NOAEL into a corrected inhalation NOAEC to assess human inhalation exposure, the NOAEL has to be corrected as follows:

 

corrected inhalatory NOAEC = oral NOAEL /AF intrerspecies * human bw / wRV * ABSoral-dog/ABS inh-human * 7 days exposure dog/5 days exposure worker)

corrected inhalatory NOAEC = (0.84 mg/kg bw/day ) / (1.4) * 70 kg bw /10 m³/person 1/1  * (7/5) = 5.88 mg/m³

 

It is assumed that oral absorption rate is 100% of that of inhalation absorption.

bw = body weight

wRV = Worker Respiratory Volume

ABSoral-dog=oral absorption rate in dog

ABSinh-human=inhalation absorption rate in humans.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a 52 week study in the dog which is considered a subchronic study and therefore, the default value of 2 for a subchronic study is applied.
AF for interspecies differences (allometric scaling):
1
Justification:
Interspecies differences were taken into account for the conversion of the dog NOAEL into a modified human NOAEC considering allometric scaling for the respiratory volumes (modification of the dose descriptor starting point). Thus, no additional AF is applicable.

AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default AF for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.667 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
180
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Not needed as a subacute dermal study was used for derivation of the DNEL.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study in the rabbit and therefore, the default value of 6 is applied.
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default AF for dogs according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default AF for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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:
42 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:
0.84 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
2.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a 52-week oral toxicity study in dogs (key, 1991, HLA 6111-112). To convert the dog oral NOAEL into a corrected inhalation NOAEC to assess human inhalation exposure, the NOAEL has to be corrected as follows:

 

corrected inhalatory NOAEC = oral NOAEL /AF intrerspecies * human bw / gpRV * ABSoral-dog/ABS inh-human

corrected inhalatory NOAEC = (0.84 mg/kg bw/day ) / (1.4) * 70 kg bw /20 m³/person 1/1 = 2.1 mg/m³

 

It is assumed that oral absorption rate is 100% of that of inhalation absorption.

bw = body weight

gpRV = general population Respiratory Volume

ABSoral-dog=oral absorption rate in dogs

ABSinh-human=inhalation absorption rate in humans.

 

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a 52 week study in the dog which is considered a subchronic study and therefore, the default value of 2 for a subchronic study is applied.
AF for interspecies differences (allometric scaling):
1
Justification:
Interspecies differences were taken into account for the conversion of the dog NOAEL into a modified human NOAEC considering allometric scaling for the respiratory volumes (modification of the dose descriptor starting point). Thus, no additional AF is applicable.
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default AF for the general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Most sensitive endpoint:
acute toxicity
Acute/short term exposure
Hazard assessment conclusion:
low 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:
833 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
360
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Not needed as a subacute dermal study was used for derivation of the DNEL.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
6
Justification:
The DNEL is based on a subacute study in the rabbit and therefore, the default value of 6 is applied.
AF for interspecies differences (allometric scaling):
2.4
Justification:
Default AF for dogs according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default AF for the general population according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12 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):
70
Dose descriptor starting point:
NOAEL
Value:
0.84 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
2
Justification:
The DNEL is based on a 52 week study in the dog which is considered a subchronic study and therefore, the default value of 2 for a subchronic study is applied.
AF for interspecies differences (allometric scaling):
1.4
Justification:
Default AF for dogs according to ECHA REACH Guidance.
AF for other interspecies differences:
2.5
Justification:
Default AF according to ECHA REACH Guidance.
AF for intraspecies differences:
10
Justification:
Default AF for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
DNEL is based on a high-quality study.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low 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:
low hazard (no threshold derived)

Additional information - General Population