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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.29 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
NOAEC
Value:
22 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeated-dose toxicity study by inhalation was available
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
Subacute exposure to Chronic exposure
AF for interspecies differences (allometric scaling):
2.5
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
1
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.61 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
112.5
Modified dose descriptor starting point:
NOAEC
Value:
519.25 mg/m³
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
7.5
Justification:
ECHA REACH Guidance & ECETOC (2010)
AF for intraspecies differences:
15
Justification:
ECHA REACH Guidance & ECETOC (2010)
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.29 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
Subacute exposure to Chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.61 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
112.5
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
7.5
Justification:
ECHA REACH Guidance & ECETOC (2010)
AF for intraspecies differences:
15
Justification:
ECHA REACH Guidance & ECETOC (2010)
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
Subacute exposure to Chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
66.67 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
2.4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.67 µg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
30
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
Subacute exposure to Chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
1
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.89 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
other: NOAEL
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

For acute toxicity, NOAEL could be derived from the LD0 obtained by oral route and dermal route. For acute inhalation toxicity, according to ECETOC (2010) and Rusch et al. (2009), it is acceptable to take 1/3 of a LC50 that will be considered as the non-lethal dose. Therefore, the non-lethal dose will be 4650 mg/m3 / 3 = 1550 mg/m3. This non-lethal dose will be considered as the NOAEL for both systemic and local effects. This NOAEL then have to be converted considering the differences in exposure between the test animals (rats) and workers. An adjustment factor of 3 was eventually applied to the inter- and intraspecies AF in accordance with ECETOC (2010) in order to obtain a conservative DNEL.

For long-term exposure, only an assessment of the toxicity of the substance following a repeated dermal exposure was available. It was used to perform a route-to-route extrapolation from the dermal route to inhalation. In order to be conservative and as no actual absorption values are available, it has been decided to consider that dermal absorption in the rat was 50% less effective than the human absorption by inhalation, while it has been determined that inhalation and dermal absorption should be similar.

The assessment was considered as a short-term toxicity study.

ECETOC (2010) Guidance on Assessment Factors to Derive a DNEL.

Rusch G, Bast C, Cavender F (2009) Establishing a point of departure for risk assessment using acute inhalation toxicology data. Regul Toxicol Pharmacol. Aug;54(3):247-55

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.07 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Value:
10.86 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeated-dose toxicity study by inhalation was available
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
Subacute exposure to Chronic exposure
AF for interspecies differences (allometric scaling):
2.5
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
10
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
1
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.15 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
225
Modified dose descriptor starting point:
NOAEC
Value:
258.33 mg/m³
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
7.5
Justification:
ECHA REACH Guidance & ECETOC (2010)
AF for intraspecies differences:
30
Justification:
ECHA REACH Guidance & ECETOC (2010)
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.07 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
Subacute exposure to Chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.15 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
225
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
7.5
Justification:
ECHA REACH Guidance & ECETOC (2010)
AF for intraspecies differences:
30
Justification:
ECHA REACH Guidance & ECETOC (2010)
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.04 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
25 mg/kg bw/day
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33.33 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
2.4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.33 µg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
60
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
Subacute exposure to Chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
1
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.94 mg/cm²
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
other: NOAEL
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
12.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No repeated-dose toxicity study by oral route was available
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
ECHA REACH Guidance

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

For acute toxicity, NOAEL could be derived from the LD0 obtained by oral route and dermal route. For acute inhalation toxicity, according to ECETOC (2010) and Rusch et al. (2009), it is acceptable to take 1/3 of a LC50 that will be considered as the non-lethal dose. Therefore, the non-lethal dose will be 4650 mg/m3 / 3 = 1550 mg/m3. This non-lethal dose will be considered as the NOAEL for both systemic and local effects. This NOAEL then have to be converted considering the differences in exposure between the test animals (rats) and workers. An adjustment factor of 3 was eventually applied to the inter- and intraspecies AF in accordance with ECETOC (2010) in order to obtain a conservative DNEL.

For long-term exposure, only an assessment of the toxicity of the substance following a repeated dermal exposure was available. It was used to perform a route-to-route extrapolation from the dermal route to inhalation and oral route. In order to be conservative and as no actual absorption values are available, it has been decided to consider that dermal absorption in the rat was 50% less effective than the human absorption by inhalation and by oral route, while it has been determined that inhalation, oral, and dermal absorption should be similar.

The assessment was considered as a short-term toxicity study.

ECETOC (2010) Guidance on Assessment Factors to Derive a DNEL.

Rusch G, Bast C, Cavender F (2009) Establishing a point of departure for risk assessment using acute inhalation toxicology data. Regul Toxicol Pharmacol. Aug;54(3):247-55