Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
123.42 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):
10
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 234.21 mg/m³
Explanation for the modification of the dose descriptor starting point:

The oral NOAEL in a rat 90- day study under OECD 408 was 300 mg/kg/day for male 1000 for female rats. The findings driving the NOAEL for male rats was due the a2u, which is only found in males rat, and not in any other species or sex of animals. No adverse effects were found in females. To compensate for the lack of adversity in females, and for findings only relevant to male rats in the males, the "remaining intraspecies" value was adjusted from 2.5x to 1

 

The NOAEL of 1000 mg/kg/day was converted to an inhalation dose using the conversion factor of 0.38 m3 /kg BW/8 hours. Further adjustments are made for light work (0.67) and for 100% vs. 50% bioavailability and 1.4x for a 7 day experimental exposure to a 5 -day workweek. This results in the modified dose descriptor of 1234.21 mg/m3

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Standard value for subchronic to chronic duration
AF for other interspecies differences:
1
Justification:
The oral NOAEL in a rat 90- day study under OECD 408 was 300 mg/kg/day for male 1000 for female rats. The findings driving the NOAEL for male rats was due the a2u, which is only found in males rat, and not in any other species or sex of animals. No adverse effects were found in females. To compensate for the lack of adversity in females, and for findings only relevant to male rats in the males, the "remaining intraspecies" value was adjusted from 2.5x to 1
AF for intraspecies differences:
5
Justification:
Standard value
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
617 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The standard derivation of the acute DNEL with DNEL(acute) = 5xDNEL(long-term) was used.

Justification:
Standard value

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:
35 mg/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):
40
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral NOAEL in a rat 90- day study under OECD 408 was 300 mg/kg/day for male 1000 for female rats. The findings driving the NOAEL for male rats was due the a2u, which is only found in males rat, and not in any other species or sex of animals. No adverse effects were found in females. To compensate for the lack of adversity in females, and for findings only relevant to male rats in the males, the "remaining intraspecies" value was adjusted from 2.5x to 1

 

The NOAEL of 1000 mg/kg/day was adjusted by a factor of 1.4x for a 7 day experimental exposure to a 5 -day work week. The modified dose descriptor was 1400 mg/kg/day

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Standard value for subchronic to chronic duration
AF for interspecies differences (allometric scaling):
4
Justification:
Standard value
AF for other interspecies differences:
1
Justification:
The oral NOAEL in a rat 90- day study under OECD 408 was 300 mg/kg/day for male 1000 for female rats. The findings driving the NOAEL for male rats was due the a2u, which is only found in males rat, and not in any other species or sex of animals. No adverse effects were found in females. To compensate for the lack of adversity in females, and for findings only relevant to male rats in the males, the "remaining intraspecies" value was adjusted from 2.5x to 1
AF for intraspecies differences:
5
Justification:
Standard value
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
175 mg/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):
100
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The standard derivation of the acute DNEL with DNEL(acute) = 5xDNEL(long-term) was used.

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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

Worker

The data from a 90-day repeat dose study in rats is used for DNEL calculation. The NOAEL of 1000 mg/kg/day was based on kidney effects that are based on a mechanism that is not relevant to humans or other animals other than male rats.

Worker DNEL long-term systemic for oral route

No oral DNEL for workers 

 

Worker DNEL long-term systemic for dermal route

 

Start point:        NOAEL:                1000mg/kg bw/day (based on oral 90-day rat study).

Differences in absorption:           Abs (oral-rat) / Abs (dermal-human):                                     1

Correction for 7 day/week dosing in the study to a 5 day work week:                                      1.4

 

=>Corrected NOAEL:                    1400 mg/kg bw/day

 

Interspecies differences:  Allometric scaling:                                                                             4

Remaining interspecies differences:                                                                                          1

Intraspecies differences:                                                                                                          5

Differences in duration of exposure (subchronic study to chronic):                                            2

Dose response and endpoint specific/severity issues:                                                                1

Quality of database:                                                                                                                1

Overall factor (product of individual factors):                                                                   40

 

=>Worker DNEL long-term for dermal route-systemic:                                                 35 mg/kg bw/day

 

Worker DNEL long-term systemic for inhalation route

 

Start point:       NOAEL 1000 mg/kg bw/day (based on oral 90-day rat study).

Respiratory volume rat (sRV) (worker (8 h): 1/0.38):                                                          2631.5 mg/m3

Correction for respiratory bioavailability (100%/50%):                                                             1315.7 mg/m3

Corrected for 7 days of animal dosing to a 5 day work week (1.4x value):                               1842.11 mg/m3

Differences in respiratory volume (default factor "light activity worker"):                               1234.21 mg/m3

Corrected NOAEC:                                                                                                              1234.21 mg/m3

 

Remaining interspecies differences:                                                                                           1

Intraspecies differences:                                                                                                           5

Differences in duration of exposure:                                                                                          2

Dose response and endpoint specific/severity issues:                                                                 1

Quality of database:                                                                                                                 1

Overall factor (product of individual factors):                                                                     10

 

=>Worker DNEL long-term for inhalation route-systemic:                                              123.42 mg/m3

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21.7 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):
80
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
434.78 mg/m³
Explanation for the modification of the dose descriptor starting point:

The oral NOAEL in a rat 90- day study under OECD 408 was 300 mg/kg/day for male 1000 for female rats. The findings driving the NOAEL for male rats was due the a2u, which is only found in males rat, and not in any other species or sex of animals. No adverse effects were found in females. To compensate for the lack of adversity in females, and for findings only relevant to male rats in the males, the "remaining intraspecies" value was adjusted from 2.5x to 1

 

The NOAEL of 1000 mg/kg/day was converted to an inhalation dose using the conversion factor of 1.15 m3 /kg BW/24 hours. Further adjustments are made for 100% vs. 50% bioavailability. This results in the modified dose descriptor of 434.78 mg/m3

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Standard value for subchronic to chronic duration
AF for other interspecies differences:
1
Justification:

The oral NOAEL in a rat 90- day study under OECD 408 was 300 mg/kg/day for male 1000 for female rats. The findings driving the NOAEL for male rats was due the a2u, which is only found in males rat, and not in any other species or sex of animals. No adverse effects were found in females. To compensate for the lack of adversity in females, and for findings only relevant to male rats in the males, the "remaining intraspecies" value was adjusted from 2.5x to 1
AF for intraspecies differences:
10
Justification:
Standard value
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
108.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

Standard derivation of acute DNEL was used.i.e. Acute DNEL = Long term DNEL *5

 

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:
12.5 mg/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):
80
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral NOAEL in a rat 90- day study under OECD 408 was 300 mg/kg/day for male 1000 for female rats. The findings driving the NOAEL for male rats was due the a2u, which is only found in males rat, and not in any other species or sex of animals. No adverse effects were found in females. To compensate for the lack of adversity in females, and for findings only relevant to male rats in the males, the "remaining intraspecies" value was adjusted from 2.5x to 1

 

The NOAEL of 1000 mg/kg/day was not adjusted as the study was dosed 7 days/week. The modified dose descriptor was 1000 mg/kg/day

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Standard value for subchronic to chronic:
AF for interspecies differences (allometric scaling):
4
Justification:
Standard value
AF for other interspecies differences:
1
Justification:

The oral NOAEL in a rat 90- day study under OECD 408 was 300 mg/kg/day for male 1000 for female rats. The findings driving the NOAEL for male rats was due the a2u, which is only found in males rat, and not in any other species or sex of animals. No adverse effects were found in females. To compensate for the lack of adversity in females, and for findings only relevant to male rats in the males, the "remaining intraspecies" value was adjusted from 2.5x to 1
AF for intraspecies differences:
10
Justification:
Standard value
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
62.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

Standard derivation of acute DNEL was used.i.e. Acute DNEL = Long term DNEL *5

 

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
12.5 mg/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):
80
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral NOAEL in a rat 90- day study under OECD 408 was 300 mg/kg/day for male 1000 for female rats. The findings driving the NOAEL for male rats was due the a2u, which is only found in males rat, and not in any other species or sex of animals. No adverse effects were found in females. To compensate for the lack of adversity in females, and for findings only relevant to male rats in the males, the "remaining intraspecies" value was adjusted from 2.5x to 1

 

The NOAEL of 1000 mg/kg/day was not adjusted as the study was dosed 7 days/week. The modified dose descriptor was 1000 mg/kg/day

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Standard value for sub-chronic to chronic duration
AF for interspecies differences (allometric scaling):
4
Justification:
Standard value
AF for other interspecies differences:
1
Justification:

The oral NOAEL in a rat 90- day study under OECD 408 was 300 mg/kg/day for male 1000 for female rats. The findings driving the NOAEL for male rats was due the a2u, which is only found in males rat, and not in any other species or sex of animals. No adverse effects were found in females. To compensate for the lack of adversity in females, and for findings only relevant to male rats in the males, the "remaining intraspecies" value was adjusted from 2.5x to 1
AF for intraspecies differences:
10
Justification:
Standard value
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
62.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

Standard derivation of acute DNEL was used.i.e. Acute DNEL = Long term DNEL *5

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General Population

General Population DNEL long-term systemic for oral route

 

Start point:        NOAEL:                1000 mg/kg bw/day (based on oral 90-day rat study).

Differences in absorption Abs (oral-rat) / Abs (oral-human):                                               1

 

=> Corrected NOAEL:     1000 mg/kg bw/day

 

Interspecies differences:Allometric scaling:                                                                         4

Remaining interspecies differences:                                                                                     1

Intraspecies differences:                                                                                                     10

Differences in duration of exposure (subchronic study to chronic study):                           2

Dose response and endpoint specific/severity issues:                                                           1

Quality of database:                                                                                                           1

Overall factor (product of individual factors):                                                               80

 

=>General Population DNEL long-term for oral route-systemic:                              12.5 mg/kg bw/day

 

General Population DNEL long-term systemic for dermal route

 

Start point:        NOAEL:                              1000 mg/kg bw/day (based on oral 90-day rat study)

Differences in absorption:                           Abs (oral-rat) / Abs (dermal-human):1

 

=>Corrected NOAEL:                                                                                                    1000 mg/kg bw/day

 

Interspecies differences:             Allometric scaling:                                                             4

Remaining interspecies differences:                                                                                     1

Intraspecies differences:                                                                                                     10

Differences in duration of exposure (subchronic study to chronic):                                       2

Dose response and endpoint specific/severity issues:                                                           1

Quality of database:                                                                                                           1

Overall factor (product of individual factors):                                                               80

=>General Population DNEL long-term for dermal route-systemic:                          12.5 mg/kg bw/day

 

General Population DNEL long-term systemic for inhalation route

Start point:                                        NOAEL 1000 mg/kg bw/day (based on oral 90-day rat study).

Respiratory volume rat (sRV) (worker (8 h): 1/1.15):                                                         869.57 mg/m3

Correction for respiratory bioavailability (100%/50%):                                                       434.78 mg/m3

Corrected NOAEC:                                                                                                        434.78 mg/m3

 

Remaining interspecies differences:                                                                                     1

Intraspecies differences:                                                                                                     10

Differences in duration of exposure:                                                                                    2

Dose response and endpoint specific/severity issues:                                                           1

Quality of database:                                                                                                           1

Overall factor (product of individual factors):                                                               20

=>General PopulationDNEL long-term for inhalation route-systemic:                       21.7 mg/m3