Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 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):
37.5
Modified dose descriptor starting point:
LOAEC
Value:
7.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
The inhalation DNEL derivation was done according to the corresponding ECHA Technical Guidance document ("Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health"). As dose descriptor starting point a LOAEL derived from a chronic oral toxicity study in mouse (Brown et al. 1978, key study, see Endpoint record 7.5.1.001) was used. This oral LOAEL (7 mg/kg/day) was first converted into a corrected inhalatory LOAEC to assess human inhalatory exposure ("Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health", page 27, assumption of 100 % absorption). The resulting value for the LOAEC (mouse) was 11.11 mg/m³ (8 h, dividing 7 mg/kg by 0.63 m³/kg, the standard respiratory volume for mice (2.35 L/h, average weight 0.03 kg -> 1.31 L/min/kg; for 8 h -> 0.63 m³/kg)). This LOAEC (mouse) was then converted to the LOAEC (worker, 8 h) by multiplying the corresponding respiration factor (standard respiratory volume human/worker respiratory volume (8 h); 6.7 m³/10 m³). The resulting corrected inhalatory LOAEC (worker, 8h) was 7.4 mg/m³.
AF for dose response relationship:
3
Justification:
Starting point is a LOAEC instead of a NOAEC. Since the quality of the study in general is good, the lowest AF necessary for a non-NOAEC/NOAEL starting point was chosen (min. 3, max 10). [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 36]
AF for differences in duration of exposure:
1
Justification:
The underlying study was a chronic oral toxicity study in mouse (Brown et al. 1978, key study, see Endpoint record 7.5.1.001), therefore the default AF 1 was chosen. [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 38, Table R.8-6]
AF for interspecies differences (allometric scaling):
1
Justification:
The AF Interspecies (allometric scaling mouse, 7) has already been used by the conversion from LOAEC (mouse) to LOAEC (worker). Therefore no additional AF for interspecies differences applies. [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health]
AF for other interspecies differences:
2.5
Justification:
AF for remaining differences [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 38, Table R.8-6]
AF for intraspecies differences:
5
Justification:
AF for worker [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 38, Table R.8-6]
AF for the quality of the whole database:
1
Justification:
Good quality of the database (completeness, consistency, standard information requirements), therefore the default AF 1 was applied. [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 36]
AF for remaining uncertainties:
1
Justification:
There were no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
0.027 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
262.5
Modified dose descriptor starting point:
LOAEL
Value:
7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The dermal DNEL derivation was done according to the corresponding ECHA Technical Guidance document ("Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health"). As dose descriptor starting point a LOAEL derived from a chronic oral toxicity study in mouse (Brown et al. 1978, key study, see Endpoint record 7.5.1.001) was used with an assumed absorption of 100 % for the route-to-route extrapolation (oral -> dermal).
AF for dose response relationship:
3
Justification:
Starting point is a LOAEL instead of a NOAEL. Since the quality of the study in general is good, the lowest AF necessary for a non-NOAEC/NOAEL starting point was chosen (min. 3, max 10). [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 36]
AF for differences in duration of exposure:
1
Justification:
The underlying study was a chronic oral toxicity study in mouse (Brown et al. 1978, key study, see Endpoint record 7.5.1.001), therefore the default AF 1 was chosen. [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 38, Table R.8-6]
AF for interspecies differences (allometric scaling):
7
Justification:
Allometric scaling factor for mice. [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 30, Table R.8-3]
AF for other interspecies differences:
2.5
Justification:
AF for remaining differences [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 38, Table R.8-6]
AF for intraspecies differences:
5
Justification:
AF for worker [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 38, Table R.8-6]
AF for the quality of the whole database:
1
Justification:
Good quality of the database (completeness, consistency, standard information requirements), therefore the default AF 1 was applied. [ECHA Guidance document Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, page 36]
AF for remaining uncertainties:
1
Justification:
There were no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic 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

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

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)

General Population - Hazard via oral route

Systemic 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 for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population