Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
75 mg/m³
Explanation for the modification of the dose descriptor starting point:

Regarding absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested on page 19 of Guidance Document, Chapter R.8 (2012). To convert the oral NOAEL into inhalatory NOAEC, a mouse default respiratory volume was used corresponding to the daily duration of worker exposure (sRVmice: 0.67 m3/kg bw/8 h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3 for an 8-h exposure period) and under conditions of light activity (wRV: 10 m3 for an 8-h exposure period).

Thus, the corrected dose descriptor for inhalation is [150 mg/kg bw/day] x [1 / 0.67 m3/kg bw/8 h] x [6.7 m3 / 10 m3] /2 = 75 mg/m3 for workers.

AF for dose response relationship:
1
Justification:
The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance
AF for differences in duration of exposure:
1
Justification:
The NOAEL was determined from a chronic study. Table R.8-5 ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
Table R.8-4 ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
Default factor for worker. Table R.8-6 ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
Default factor for good/standard quality of the database taken into account completeness, consistency and the standard information requirements for the tonnage band
AF for remaining uncertainties:
1
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:
medium hazard (no threshold derived)
DNEL related information
AF for interspecies differences (allometric scaling):
1
Acute/short term exposure
Hazard assessment conclusion:
medium 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:
1.71 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
87.5
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. Since a maximal absorption already occurred by oral route, no additional factor was introduced.

AF for dose response relationship:
1
Justification:
The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance
AF for differences in duration of exposure:
1
Justification:
The NOAEL was determined from a chronic study. Table R.8-5 ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
7
Justification:
Default allometric scaling factor for mice. Table R.8-4 ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
Default factor for worker. Table R.8-6 ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
Default factor for good/standard quality of the database taken into account completeness, consistency and the standard information requirements for the tonnage band
AF for remaining uncertainties:
1
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:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high 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:
1.5 mg/m³
Most sensitive endpoint:
carcinogenicity
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:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
37.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Regarding absorption, in the absence of reliable data for both the starting route (oral) and the end route (inhalation), worst case assumptions were made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL. Thus, in the case of oral-to- inhalation extrapolation, it is proposed to include a default factor of 2, i.e. the absorption percentage by oral route is half that of the inhalation absorption as suggested on page 19 of Guidance Document, Chapter R.8 (2012). To convert the oral NOAEL into inhalatory NOAEC, a mouse default respiratory volume was used corresponding to the daily duration of human exposure (sRVmice: 2 m3/kg bw/24 h). Thus, the corrected dose descriptor for inhalation is [150 mg/kg bw/day] / [2 m3/kg bw/day] /2. Thus, the corrected dose descriptor for inhalation is 37.5mg/m3 for consumers.

AF for dose response relationship:
1
Justification:
The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance
AF for differences in duration of exposure:
1
Justification:
The NOAEL was determined from a chronic study. Table R.8-5 ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
Table R.8-4 ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
Default factor for general population. Table R.8-6 ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
Default factor for good/standard quality of the database taken into account completeness, consistency and the standard information requirements for the tonnage band
AF for remaining uncertainties:
1
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:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium 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:
0.85 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
175
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For potential dermal exposure, route-to-route extrapolation from the oral NOAEL value was considered appropriate. Since a maximal absorption already occurred by oral route, no additional factor was introduced.

AF for dose response relationship:
1
Justification:
The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance
AF for differences in duration of exposure:
1
Justification:
The NOAEL was determined from a chronic study. Table R.8-5 ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
7
Justification:
Default allometric scaling factor for mice. Table R.8-4 ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
Default factor for general population. Table R.8-6 ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
Default factor for good/standard quality of the database taken into account completeness, consistency and the standard information requirements for the tonnage band
AF for remaining uncertainties:
1
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:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.85 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
175
Dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not applicable
AF for dose response relationship:
1
Justification:
The dose-descriptor is a NOAEL. Table R.8-6 ECHA REACH Guidance
AF for differences in duration of exposure:
1
Justification:
The NOAEL was determined from a chronic study. Table R.8-5 ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
7
Justification:
Default allometric scaling factor for mice. Table R.8-4 ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences. Table R.8-6 ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
Default factor for general population. Table R.8-6 ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
Default factor for good/standard quality of the database taken into account completeness, consistency and the standard information requirements for the tonnage band
AF for remaining uncertainties:
1
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:
medium hazard (no threshold derived)

Additional information - General Population