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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
12.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: according to ECETOC guidance (Technical report no. 110, October 2010)
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Value:
220 mg/m³
Explanation for the modification of the dose descriptor starting point:
no evidence is available that route-to-route extrapolation is not possible
AF for dose response relationship:
1
Justification:
reliable NOAEL
AF for differences in duration of exposure:
6
Justification:
assuming chronic exposure of worker
AF for interspecies differences (allometric scaling):
1
Justification:
no correction for caloric demand applicable for inhalation
AF for other interspecies differences:
1
Justification:
not relevant
AF for intraspecies differences:
3
Justification:
differences in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
reliable studies available for each endpoint required
AF for remaining uncertainties:
1
Justification:
not relevant
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
1.1 mg/kg bw/day
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
90
Modified dose descriptor starting point:
other: EC3
Value:
96.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not relevant
AF for dose response relationship:
3
Justification:
from LOAEL to NAEL
AF for differences in duration of exposure:
1
Justification:
assuming chronic exposure of worker
AF for interspecies differences (allometric scaling):
10
Justification:
rat to human, specific for skin sensitisation
AF for other interspecies differences:
1
Justification:
not relevant
AF for intraspecies differences:
3
Justification:
differences in sensitivity among workers
AF for the quality of the whole database:
1
Justification:
reliable studies available for each endpoint required
AF for remaining uncertainties:
1
Justification:
not relevant
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Dermal long term systemic:

The NOAEL of the reproduction/developmental screening study and the EC3 of the LLNA skin sensitsation study have both been used as starting point for derivation of the DNEL. The DNEL based on the EC3 appeared to be the worst case, and therefore is used in risk assessment.

Starting point: NOAEL of 250 mg/kg bw/day in a screening reproduction/developmental oral toxicity study in rats.

Correction dermal NOAEL: 250 x 50/10a= 1250 mg/kg bw/day

aoral/dermal absorption

 

Safety factors:

-          Interspecies extrapolation: 4 (rat to human)

-          Intraspecies extrapolation: 3

-          Exposure duration: 6 (assuming chronic exposure of the worker)

-          Dose response: 1

-          Quality of the data base: 1

Total safety factor: 72

Based on the above, the long-term DNEL for systemic effects after dermal exposure of the worker is 17.4 mg/kg bw/day.

 

Second starting point: EC3=11.6% (is a LOAEL) in a skin sensitization study in mice.

See above, for specific derivation. Based on this, the long-term DNEL for systemic effects after dermal exposure of the worker is set at 1.1 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: according to ECETOC guidance (Technical report no. 110, October 2010)
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Value:
109 mg/m³
Explanation for the modification of the dose descriptor starting point:
no evidence is available that route-to-route extrapolation is not possible
AF for dose response relationship:
1
Justification:
reliable NOAEL
AF for differences in duration of exposure:
6
Justification:
assuming chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
no correction for caloric demand for inhalation
AF for other interspecies differences:
1
Justification:
not relevant
AF for intraspecies differences:
5
Justification:
differences in sensitivity among general population
AF for the quality of the whole database:
1
Justification:
reliable studies available for each endpoint required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
0.64 mg/kg bw/day
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEL
Value:
96.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not relevant
AF for dose response relationship:
3
Justification:
from LOAEL to NAEL
AF for differences in duration of exposure:
1
Justification:
assuming chronic exposure
AF for interspecies differences (allometric scaling):
10
Justification:
rat to human, specific for skin sensitsation
AF for other interspecies differences:
1
Justification:
not relevant
AF for intraspecies differences:
5
Justification:
differences in sensitivity among general population
AF for the quality of the whole database:
1
Justification:
reliable studies available for each endpoint required
AF for remaining uncertainties:
1
Justification:
not relevant
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: according to ECETOC guidance (Technical report no. 110, October 2010)
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not applicable
AF for dose response relationship:
1
Justification:
reliable NOAEL
AF for differences in duration of exposure:
6
Justification:
assuming chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
1
Justification:
not relevant
AF for intraspecies differences:
5
Justification:
differences in sensitivity among general population
AF for the quality of the whole database:
1
Justification:
reliable studies available for each endpoint required
AF for remaining uncertainties:
1
Justification:
not relevant
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

Dermal long term systemic:

The NOAEL of the reproduction/developmental screening study and the EC3 of the LLNA skin sensitsation study have both been used as starting point for derivation of the DNEL. The DNEL based on the EC3 appeared to be the worst case, and therefore is used in risk assessment.

Starting point: NOAEL of 250 mg/kg bw/day in a screening reproduction/developmental oral toxicity study in rats.

Correction dermal NOAEL: 250 x 50/10a= 1250 mg/kg bw/day

aoral/dermal absorption

 

Safety factors:

-          Interspecies extrapolation: 4 (rat to human)

-          Intraspecies extrapolation: 5

-          Exposure duration: 6 (assuming chronic exposure of the worker)

-          Dose response: 1

-          Quality of the data base: 1

Total safety factor: 120

Based on the above, the long-term DNEL for systemic effects after dermal exposure of the general population is 10.4 mg/kg bw/day.

 

Second starting point: EC3=11.6% (is a LOAEL) in a skin sensitization study in mice.

See above, for specific derivation. Based on this, the long-term DNEL for systemic effects after dermal exposure of the general population is set at 0.64 mg/kg bw/day.