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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.65 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
54
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
35.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.

Starting point: LOAEL of 100 mg/kg bw/day in a 28-day repeated dose toxicity study in rat.

Conversion of an oral LOAEL into a corrected LOAEC:

For workers (8h exposure/day), the corrected inhalatory LOAEC = oral LOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human * sRVhuman/wRV

           = 100 * 1/0.38 m3/kg/8h * ABSoral-rat /ABSinhal-human * 6.7 m3(8h)/10 m3(8h)

           = 100 * 1/0.38 m3/kg/8h * 10%/50% * 6.7 m3 (8h)/10 m3(8h)

= 100 /0.38 * 10%/50% * (6.7/10) = 35.3 mg/m3.

 

With ABS: Absorption, sRV: Standard Respiratory Volume; wRV: Worker Respiratory Volume;

ABSoral-rat /ABSinhal-human= 100/100= 1, assuming no differences in inhalation absorption between rats and humans.

AF for dose response relationship:
3
Justification:
Value is LOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure worker
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for other interspecies differences:
1
Justification:
No remaining differences.
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
0.46 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
216
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite.Correction dermal LOAEL: 100 x 10/10a= 100 mg/kg bw/day (a% oral/dermal absorption)

AF for dose response relationship:
3
Justification:
Value is LOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure worker
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

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:
0.19 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
90
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEC
Value:
17.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.

For the general population (24h exposure/day), the corrected inhalatory LOAEC = oral LOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human

 

           = 100 * 1/1.15 m3/kg * ABSoral-rat /ABSinhal-human

 

           = 100 * 1/1.15 m3/kg * 10/50 = 17.4 mg/m3

 

With ABS: Absorption, sRV: Standard Respiratory Volume;

ABSoral-rat /ABSinhal-human= 10/50= 1, assuming no differences in inhalation absorption between rats and humans.

AF for dose response relationship:
3
Justification:
Value is LOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure general population
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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:
0.28 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
360
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite.Correction dermal LOAEL: 100 x 10/10a= 100 mg/kg bw/day (a% oral/dermal absorption).

AF for dose response relationship:
3
Justification:
Value is LOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure worker
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within general population
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
360
Dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

As the starting point is an oral repeated dose study, no modification is needed.

 

AF for dose response relationship:
3
Justification:
Value is LOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from subacute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity among general population
AF for the quality of the whole database:
1
Justification:
Reliable studies used
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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