Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.05 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
Dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
528.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Dose descriptor starting point: NOAEL from OECD 407 study via oral gavage

Modified dose descriptor starting point: NOAEC (Most sensitive endpoint used)

Inhalation NOAEC = oral NOAEL*(1/0.38 m3/kg/d)*0.67*(ABSoral/ABSinh.)

(ABSoral/ABSinh.) = 0.5

AF for dose response relationship:
1
Justification:
ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
The relevant dose descriptors considered for DNEL derivation is a NOAEL value from a gavage repeated dose toxicity study (OECD TG 407, reliability 1).
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
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No acute toxicity hazard (leading to C&L) has been identified for the target substance following oral and dermal exposure. Therefore, according to ECHA R8 Guidance, no DNEL (acute) should be set.

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 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
Dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAELhuman-dermal

= NOAELrat -oral*(ABSrat-oral÷ABShuman-dermal)

= 600 mg/kg/d *ratio

 

Absorptionrat-oral= 2*Absorptionhuman-dermal

Justifications for low dermal absorption were included in CSR

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:
5
Justification:
ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
ECHA REACH Guidance
Justification:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No hazard identified

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.74 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
Dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
260.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Dose descriptor starting point:NOAEL from OECD 407 study via oral gavage

Modified dose descriptor starting point:NOAEC (Most sensitive endpoint used)

Inhalation NOAEC = oral NOAEL/1.15m3/kg/d*(ABSoral/ABSinh.)

(ABSoral/ABSinh.) = 0.5

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):
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:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No acute toxicity hazard (leading to C&L) has been identified for the target substance following oral and dermal exposure. Therefore, according to ECHA R8 Guidance, no DNEL (acute) should be set.

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAELhuman-dermal

= NOAELrat -oral*(ABSrat-oral÷ABShuman-dermal)

 

Absorptionrat-oral= 2*Absorptionhuman-dermal

Justifications for dermal absorption were included in CSR

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:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No hazard identified

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 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
DNEL value:
600 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The relevant dose descriptors considered for DNEL derivation is a NOAEL value from a gavage 28-day repeated dose toxicity study (OECD TG 407, reliability 1).In this study the highest dose level of 600 mg/kg bw/day resulted in premature deaths of three females. These deaths were considered to be related to the irritant properties of the test item and gavage-related reflux rather than an indication of its systemic toxicity. The NOAEL is therefore 600 mg/kg bw/day in rats.

AF for dose response relationship:
1
Justification:
Key study used a dose range that demonstrated a clear dose-response relationship
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:
No remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No hazard identified

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population