Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21.16 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):
25
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
528.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

Modification of the starting point (R.8 Figure R.8 -3):

Corrected inhalatory N(L)OAEC = oral N(L)OAEL*(1/sRVrat)*ABSoral-rat/ABSinh-human)*(sRVhuman/wRV)

= oral N(L)OAL*(1/0.38 m3/kg/d)*(1/1)*6.7m3(8h)/10 m3 (8h))

ABS: Absoprtion

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume

ABSoral-rat: 1 [-]: worst case default

ABSinh-human: 1 [-]: worst case default

AF for dose response relationship:
1
Justification:
No issues in relevance or reliability of dose response: REACH guidance R.8 (default)
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic: REACH guidance R.8 (default)
Justification:
Not relevant for corrected inhalation DNEL: REACH guidance R.8 (default)
AF for other interspecies differences:
2.5
Justification:
Interspecies remaining differences: REACH guidance R.8 (default)
AF for intraspecies differences:
5
Justification:
Worker: REACH guidance R.8 (default)
AF for the quality of the whole database:
1
Justification:
No significant reduction in relevance or reliability across the database: REACH guidance R.8 (default)
Justification:
No remaining uncertainties.
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:
3 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
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No absorption data is available, therefore a worst case modification factor of 1 is used: REACH guidance

R.8 (default).

AF for dose response relationship:
1
Justification:
No issues in relevance or reliability of dose response: REACH guidance R.8 (default)
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic: REACH guidance R.8 (default)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to Human: REACH guidance R.8 (default)
AF for other interspecies differences:
2.5
Justification:
Interspecies remaining differences: REACH guidance R.8 (default)
AF for intraspecies differences:
5
Justification:
Worker: REACH guidance R.8 (default)
AF for the quality of the whole database:
1
Justification:
No significant reduction in relevance or reliability across the database: REACH guidance R.8 (default)
Justification:
No remaining uncertainties.
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

1. Identification of relevant dose descriptor

In an OECD 408 study performed in rats, the substance did not cause mortalities. Lowered body weight as well as increased liver and kidney weight and centrolubular hypertrophy were observed. The NOAL is considered to be 300 mg/kg bw.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

Calculation of DNEL bases upon Guidance Document on Dermal Absorption, European Commission, 2004 and Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, may 2008

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.22 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):
50
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
261 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected inhalatory N(L)OAEC = oral N(L)OAEL*(1/sRVrat)*ABSoral-rat/ABSinh-human)

= oral N(L)OAL*(1/1.15 m3/kg/d)*(1/1)

ABS: Absoprtion

sRV: standard Respiratory Volume

ABSoral-rat: 1 [-]: worst case default

ABSinh-human: 1 [-]: worst case default

AF for dose response relationship:
1
Justification:
No issues in relevance or reliability of dose response: REACH guidance R.8 (default)
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic: REACH guidance R.8 (default)
Justification:
Not relevant for corrected inhalation DNEL: REACH guidance R.8 (default)
AF for other interspecies differences:
2.5
Justification:
Interspecies remaining differences: REACH guidance R.8 (default)
AF for intraspecies differences:
10
Justification:
General population: REACH guidance R.8 (default)
AF for the quality of the whole database:
1
Justification:
No significant reduction in relevance or reliability across the database: REACH guidance R.8 (default)
Justification:
No remaining uncertainties.
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:
1.5 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):
200
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No absorption data is available, therefore a worst case modification factor of 1 is used: REACH guidance R.8 (default)

AF for dose response relationship:
1
Justification:
No issues in relevance or reliability of dose response: REACH guidance R.8 (default)
AF for differences in duration of exposure:
2
Justification:
Subacute to Chronic: REACH guidance R.8 (default)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to Human: REACH guidance R.8 (default)
AF for other interspecies differences:
2.5
Justification:
Interspecies remaining differences: REACH guidance R.8 (default)
AF for intraspecies differences:
10
Justification:
General population: REACH guidance R.8 (default)
AF for the quality of the whole database:
1
Justification:
No significant reduction in relevance or reliability across the database: REACH guidance R.8 (default)
Justification:
No remaining uncertainties.
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 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):
200
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
AF for dose response relationship:
1
Justification:
No issues in relevance or reliability of dose response: REACH guidance R.8 (default)
AF for differences in duration of exposure:
2
Justification:
Subchronic to chronic: REACH guidance R.8 (default)
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to Human: REACH guidance R.8 (default)
AF for other interspecies differences:
2.5
Justification:
Interspecies remaining differences: REACH guidance R.8 (default)
AF for intraspecies differences:
10
Justification:
General population: REACH guidance R.8 (default)
AF for the quality of the whole database:
1
Justification:
No significant reduction in relevance or reliability across the database: REACH guidance R.8 (default)
Justification:
No remaining uncertainties.
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

1. Identification of relevant dose descriptor

In an OECD 408 study performed in rats, the substance did not cause mortalities. Lowered body weight as well as increased liver and kidney weight and centrolubular hypertrophy were observed. The NOAL is considered to be 300 mg/kg bw.

2. Mode of action

No non-threshold mode of action is associated with the test substance. In particular, the test substance has no genotoxic potential.

Calculation of DNEL bases upon Guidance Document on Dermal Absorption, European Commission, 2004 and Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health, may 2008