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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
166.67 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Value:
1 000 mg/m³
Explanation for the modification of the dose descriptor starting point:

No information form long term inhalation study available

AF for dose response relationship:
1
Justification:
AF according to ECETOC report
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub chronic to chronic) 2 AF according to ECETOC report
AF for interspecies differences (allometric scaling):
1
Justification:
Already in starting point correction
AF for other interspecies differences:
1
Justification:
AF according to ECETOC report
AF for intraspecies differences:
3
Justification:
Intraspecies (worker) 3 AF according to ECETOC report
AF for the quality of the whole database:
1
Justification:
AF according to ECETOC report
AF for remaining uncertainties:
1
Justification:
AF according to ECETOC report
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:
23.81 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report
Overall assessment factor (AF):
8.4
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

worst case assumption (not necessary correct) NOAEL oral -> NOAEL dermal = NOAEL oral x 1(Echa assumption)

AF for dose response relationship:
1
Justification:
AF according to ECETOC report
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub chronic to chronic) 2
AF for interspecies differences (allometric scaling):
1.4
Justification:
Interspecies (AS, dog) 1.4
AF for other interspecies differences:
1
Justification:
AF according to ECETOC report
AF for intraspecies differences:
3
Justification:
Intraspecies (worker) 3 AF according to ECETOC report
AF for the quality of the whole database:
1
Justification:
AF according to ECETOC report
AF for remaining uncertainties:
1
Justification:
AF according to ECETOC report
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Only long term exposure values for worker and general population were calculated, because no concrete values (like NOAEL, LOAEL etc) are available from acute or irritation studies. The study designs of the tests conducted assessing the acute and local toxicity do

in general not allow the derivation of local or acute DNEL, as most of the test were, for example, conducted as limit tests due to animal welfare.

For long term effects a valid repeated dose animal studies is available to derive DNEL values.

In a 90-day gavage study (Bayer 2000, J. Ruf) beagle dogs were treated once daily with the registered substance.

The NOEL at 40 mg/kg bw/d (0.4%) reported in this study is based on local effects caused by oral application of the test substance at irritating concentrations (≥2%). At 200 mg/kg bw/d clinical chemistry revealed only slightly increased liver findings (weight increase, N-DEM and CYP-450 increase) but this should not be regarded as adverse effects but as increased metabolic activity of the organ (adaptive response). Therefore the NOAEL is established at 200 mg/kg bw/d.

The 90-day dog study is considered the most appropriate study for a DNEL derivation as dogs were found to be the most sensitive species based on clinical findings at 500 mg/kg bw/d.

Therefore the following values were used to derive DNELs: Dog subchronic (13 weeks; gavage) NOAEL (systemic) = 200mg/kg bw/d; NOEL (local) = 40mg/kg bw/d

As local dermal or inhalation effects can not be evaluated from local oral effects the DNEL values for local effects were not derived.

However, a qualitative risk assessment has been carried out.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
500 mg/m³
Explanation for the modification of the dose descriptor starting point:

No information form long term inhalation study available

AF for dose response relationship:
1
Justification:
AF according to ECETOC report
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub chronic to chronic) 2
AF for interspecies differences (allometric scaling):
1
Justification:
Interspecies (AS, dog) (already in starting point mod.)
AF for other interspecies differences:
1
Justification:
AF according to ECETOC report
AF for intraspecies differences:
5
Justification:
Intraspecies (general pop) AF = 5 according to ECETOC report
AF for the quality of the whole database:
1
Justification:
AF according to ECETOC report
AF for remaining uncertainties:
1
Justification:
AF according to ECETOC report
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:
14.29 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report
Overall assessment factor (AF):
14
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

worst case assumption (not necessary correct) NOAEL oral -> NOAEL dermal = NOAEL oral x 1(Echa assumption)

AF for dose response relationship:
1
Justification:
AF according to ECETOC report
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub chronic to chronic) 2
AF for interspecies differences (allometric scaling):
1.4
Justification:
Interspecies (AS, dog) 1.4
AF for other interspecies differences:
1
Justification:
AF according to ECETOC report
AF for intraspecies differences:
5
Justification:
Intraspecies (general pop) AF = 5 according to ECETOC report
AF for the quality of the whole database:
1
Justification:
AF according to ECETOC report
AF for remaining uncertainties:
1
Justification:
AF according to ECETOC report
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.29 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC technical report
Overall assessment factor (AF):
14
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

no starting point correction

AF for dose response relationship:
1
Justification:
AF according to ECETOC report
AF for differences in duration of exposure:
2
Justification:
Exposure duration (sub chronic to chronic) 2
AF for interspecies differences (allometric scaling):
1.4
Justification:
Interspecies (AS, dog) 1.4
AF for other interspecies differences:
1
Justification:
AF according to ECETOC report
AF for intraspecies differences:
5
Justification:
Intraspecies (general pop) AF = 5 according to ECETOC report
AF for the quality of the whole database:
1
Justification:
AF according to ECETOC report
AF for remaining uncertainties:
1
Justification:
AF according to ECETOC report
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Only long term exposure values for worker and general population were calculated, because no concrete values (like NOAEL, LOAEL etc) are available from acute or irritation studies. The study designs of the tests conducted assessing the acute and local toxicity do

in general not allow the derivation of local or acute DNEL, as most of the test were, for example, conducted as limit tests due to animal welfare.

For long term effects a valid repeated dose animal studies is available to derive DNEL values.

In a 90-day gavage study (Bayer 2000, J. Ruf) beagle dogs were treated once daily with the registered substance.

The NOEL at 40 mg/kg bw/d (0.4%) reported in this study is based on local effects caused by oral application of the test substance at irritating concentrations (≥2%). At 200 mg/kg bw/d clinical chemistry revealed only slightly increased liver findings (weight increase, N-DEM and CYP-450 increase) but this should not be regarded as adverse effects but as increased metabolic activity of the organ (adaptive response). Therefore the NOAEL is established at 200 mg/kg bw/d.

The 90-day dog study is considered the most appropriate study for a DNEL derivation as dogs were found to be the most sensitive species based on clinical findings at 500 mg/kg bw/d.

Therefore the following values were used to derive DNELs: Dog subchronic (13 weeks; gavage) NOAEL (systemic) = 200mg/kg bw/d; NOEL (local) = 40mg/kg bw/d

As local dermal or inhalation effects can not be evaluated from local oral effects the DNEL values for local effects were not derived.

However, a qualitative risk assessment has been carried out.