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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
118.4 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:
0.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
2.961 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, 1987). According to the ECHA guidance R8 APPENDIX R. 8-2, 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 * ratioMolWeight)/allometric scaling factor * (bw human / wRV human) *(ABSoral-dog/ABS inh-human)*(7 days exposure dog/5 days exposure worker)

corrected inhalatory NOAEC = (0.3 mg/kg bw/day * 1.41)/1.4*(70 kg bw/day /10 m³) * (1/1) * (7 days/5 days) = 2.961 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 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:
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:
no hazard identified
Most sensitive endpoint:
repeated dose 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:
33.6 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):
35
Dose descriptor starting point:
NOAEL
Value:
0.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1.176 mg/kg bw/day
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, 1987). To convert the dog oral NOAEL into a corrected dermal NOAEL to assess human dermal exposure, the NOAEL has to be corrected as follows:

 

NOAELdermal = mass corrected NOAELoral * (ABSoral-dog/ABSderm-human)* (7 days exposure dog/5 days exposure worker)  

NOAELdermal =  0.42 mg/kg bw/day * (100/50) * (7/5) = 1.176 mg/kg bw/day

 

ABS = absorption.

Dermal absorption is considered to be 50% of the oral absorption (based on oral and dermal absorption studies with the test substance). Therefore, a factor of 2 was included for oral to dermal extrapolation, as a worst case approach.

 

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:
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:
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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

For all DNEL derivations, the 52 week repeated dose toxicity dog study (key, 1987) was used since the lowest DNELS were derived with this study.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21.2 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:
0.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1.058 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, 1987). According to the ECHA guidance R8 APPENDIX R. 8-2, 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 * ratioMolWeight)/allometric scaling factor * (bw human / sRV human) *(ABSoral-dog/ABS inh-human)

corrected inhalatory NOAEC = (0.3 mg/kg bw/day * 1.41)/1.4*(70 kg bw/day /20 m³) * (1/1) = 1.0575 mg/m³

 

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

bw = body weight

sRV = 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:
no hazard identified
Most sensitive endpoint:
repeated dose 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:
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:
0.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
0.84 mg/kg bw/day
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, 1987). To convert the dog oral NOAEL into a corrected dermal NOAEL to assess human dermal exposure, the NOAEL has to be corrected as follows:

 

NOAELdermal = mass corrected NOAELoral *(ABSoral-dog/ABSderm-human)

NOAELdermal =  0.42 mg/kg bw/day * (100/50) = 0.84 mg/kg bw/day

 

ABS = absorption.

Dermal absorption is considered to be 50% of the oral absorption (based on oral and dermal absorption studies with the test substance). Therefore, a factor of 2 was included for oral to dermal extrapolation, as a worst case approach.

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 for 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:
6.1 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):
70
Dose descriptor starting point:
NOAEL
Value:
0.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
0.42 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route-to-route extrapolation was neccessary, but the NOAEL was adjusted to account for molecular differences between the target and the source substance.

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 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:
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:
no hazard identified

Additional information - General Population

For all DNEL derivations, the 52 week repeated dose toxicity dog study (key, 1987) was used since the lowest DNELS were derived with this study.