Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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):
75
Modified dose descriptor starting point:
NOAEC
Value:
264.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Using the no-adverse effect level of oral study (NOAEL = 150 mg/kg/day, 28-day, oral gavage study), the corrected starting point (NAEC) for the inhalative route is calculated according following formula for worker: = NOAEL* 1/0.38*6.7/10, where 6.7/10 mg/m³ represents the human light activity and 0.38 m³/kg bw is the standard breathing volume for the rats for 8 hours exposure for workers.

AF for dose response relationship:
1
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for differences in duration of exposure:
6
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for other interspecies differences:
2.5
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for intraspecies differences:
5
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for the quality of the whole database:
1
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
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:
0.5 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):
300
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NAEL dermal corr: = NOAEL oral x ABS(oral, rat) / ABS (dermal human) = 150 mg/kg bw/d x 1 = 150 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for differences in duration of exposure:
6
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for other interspecies differences:
2.5
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for intraspecies differences:
5
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for the quality of the whole database:
1
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The long-term worker DNEL for systemic effects is based on a subacute 28 day oral study with the test substance Y-15099 (CAS No. 220727-26-4) (Braun, 2001). The oral 28d NOAEL for rats was found to be 150 mg/kg bw/day.

Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.

 

Dermal DNEL (workers):

NAEL dermal corr: = NOAELoral x ABS(oral, rat) / ABS(dermal human) = 150 mg/kg bw/d x 1 = 150 mg/kg bw/day.

For derivation of the long-term systemic dermal DNEL, the corrected dermal NAEL was divided by the following assessment factors: Allometric scaling factor 4; interspecies factor 2.5; intraspecies factor 5; exposure duration factor 6; dose-response factor 1; quality of the database 1 => overall AF = 4 x 2.5 x 5 x 6 = 300

=> worker DNEL systemic long-term dermal = NAELdermal corr / overall AF = 150 mg/kg bw/d / 300 = 0.5 mg/kg bw/day

Inhalation DNEL (workers): Using the no-adverse effect level of oral study (NOAEL = 150 mg/kg/day, 28-day, oral gavage study), the corrected starting point (NAEC) for the inhalative route is calculated according following formula for worker: = NOAEL* 1/0.38*6.7/10, where 6.7/10 mg/m³ represents the human light activity and 0.38 m³/kg bw is the standard breathing volume for the rats for 8 hours exposure for workers. For derivation of the long-term systemic dermal DNEL, the corrected NAEC was divided by the following assessment factors: Interspecies factor 2.5; intraspecies factor 5; exposure duration factor 6; dose-response factor 1; quality of the database 1 => overall AF = 2.5 x 5 x 6 = 75 => worker DNEL systemic long-term inh. = NAECinh. corr / overall AF = 264.5 mg/m³ / 75 = 3.5 mg/

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 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):
150
Modified dose descriptor starting point:
NOAEC
Value:
130.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

Using the no-adverse effect level of oral study (NOAEL = 150 mg/kg/day, 28-day, oral gavage study), the corrected starting point (NAEC) for the inhalative route is calculated according following formula for worker: =NOAEL* 1/1.15, where 1.15 m³/kg bw is the standard breathing volume for rat for 24 hours exposure of general public.

The inhalation DNEL has been derived from the corrected starting point (NAEC) 130.4 mg/m³.

AF for dose response relationship:
1
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for differences in duration of exposure:
6
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for interspecies differences (allometric scaling):
2.5
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for intraspecies differences:
10
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for the quality of the whole database:
1
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
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:
0.25 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):
600
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NAEL dermal corr: = NOAELoral x ABS(oral, rat) / ABS(dermal human) = 150 mg/kg bw/d x 1 = 150 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for differences in duration of exposure:
6
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for interspecies differences (allometric scaling):
4
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for other interspecies differences:
2.5
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for intraspecies differences:
10
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for the quality of the whole database:
1
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 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):
600
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:

Not applicable, oral study selected as starting point.

AF for dose response relationship:
1
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for differences in duration of exposure:
6
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for interspecies differences (allometric scaling):
4
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for other interspecies differences:
2.5
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for intraspecies differences:
10
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
AF for the quality of the whole database:
1
Justification:
Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.
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

The long-term general population DNEL for systemic effects is based on a subacute 28 day oral study with the test substance Y-15099 (CAS No. 220727-26-4) (Braun, 2001). The oral 28d NOAEL for rats was found to be 150 mg/kg bw/day.

Derivation of DNELs was conducted according to the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health", ECHA, May 2008.

 

Dermal DNEL (general population):

NAEL dermal corr: = NOAELoral x ABS(oral, rat) / ABS(dermal human) = 150 mg/kg bw/d x 1 = 150 mg/kg bw/day.

For derivation of the long-term systemic dermal DNEL, the corrected dermal NAEL was divided by the following assessment factors: Allometric scaling factor 4; interspecies factor 2.5; intraspecies factor 10; exposure duration factor 6; dose-response factor 1; quality of the database 1 => overall AF = 4 x 2.5 x 10 x 6 = 600

=> general population DNEL systemic long-term dermal = NAELdermal corr / overall AF = 150 mg/kg bw/d / 600 = 0.25 mg/kg bw/day

Oral DNEL (general population):

Allometric scaling factor 4; interspecies factor 2.5; intraspecies factor 10; exposure duration factor 6; dose-response factor 1; quality of the database 1 => overall AF = 4 x 2.5 x 10 x 6 = 600

=> general population DNEL systemic long-term oral = NOAELoral / overall AF = 150 mg/kg bw/d / 600 = 0.25 mg/kg bw/day

Inhalation DNEL (general population):

Using the no-adverse effect level of oral study (NOAEL = 150 mg/kg/day, 28-day, oral gavage study), the corrected starting point (NAEC) for the inhalative route is calculated according following formula for worker: = NOAEL* 1/1.15, where 1.15 m³/kg bw is the standard breathing volume for rat for 24 hours exposure of general public.

For derivation of the long-term systemic dermal DNEL, the corrected NAEC was divided by the following assessment factors: Interspecies factor 2.5; intraspecies factor 10; exposure duration factor 6; dose-response factor 1; quality of the database 1 => overall AF = 2.5 x 10 x 6 = 150

=> worker DNEL systemic long-term inh. = NAECinh. corr / overall AF = 130.4 mg/m³ / 150 = 0.87 mg/