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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.29 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:
7.25 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 with the read across source substance (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 * molecular weight correction /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*1.233 ) / (1.4) * 70 kg bw /10 m³/person 1/1  * (7/5) = 7.25 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:
no hazard identified
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
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
2.055 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
Modified dose descriptor starting point:
NOAEL
Value:
369.9 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The most sensitive NOAEL came from a subacute dermal study with the read across source substance. The molecular weight correction factor of 1.233 was used.

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 rabbits 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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
52 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:
2.59 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 with the read across source substance (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 * molecular weight correction /AF intrerspecies * human bw / gpRV * ABSoral-dog/ABS inh-human


corrected inhalatory NOAEC = (0.84 mg/kg bw/day *1.233) / (1.4) * 70 kg bw /20 m³/person 1/1 = 2.59 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:
no hazard identified
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
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.028 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):
360
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
369.9 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL is based on a subacute study in the rabbit with the read across source substance. The molecular weight correction factor of 1.233 was used.


 

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 rabbits 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:
15 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
Modified dose descriptor starting point:
NOAEL
Value:
1.04 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 with the read across source substance (key, 1991, HLA 6111-112). The molecular weight correction factor of 1.233 was used.


 

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 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:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population