Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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)
Most sensitive endpoint:
irritation (respiratory tract)
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:
1.43 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):
210
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation (ECHA Guidance Doc R8, chapter 8.4.2, 2012).
AF for dose response relationship:
1
Justification:
As the starting point for the DNEL calculation is a NOAEL according to ECHA Guidance (November 2012), R.8.4.3.1 the default assessment factor for dose response relationship is 1.
AF for differences in duration of exposure:
4.2
Justification:
Difference in the experimental exposure duration (= subacute) and the duration of exposure for the population and scenario under consideration (= chronic) according to ECHA Guidance (November 2012) Chapter R. 8. Table R.8-5. The suggested factor of 6 for extrapolation of exposure duration subacute to chronic was corrected for difference in number of days of exposure per week (7 days/week in animal study versus 5 days/week for workers). Thus, the total AF is 6 * 0.7 = 4.2.
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA Guidance (November 2012) R.8, Table R.8-3 the allometric scaling factor for the rat when compared with humans is 4
AF for other interspecies differences:
2.5
Justification:
A factor 2.5 for remaining interspecies differences is suggested by the Guidance Document R.8 (ECHA, 2012)
AF for intraspecies differences:
5
Justification:
According to ECHA Guidance (November 2012) Chapter R.8.4.3.1 the default AF to be applied for intraspecies differences in workers is 5.
AF for the quality of the whole database:
1
Justification:
Default assessment factor for good/standard quality of database as suggested by the Guidance Document R8 (ECHA, 2012)..
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

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:
hazard unknown (no further information necessary)
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)
Most sensitive endpoint:
irritation (respiratory tract)
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:
0.5 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):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation (ECHA Guidance Doc R8, chapter 8.4.2, 2012).
AF for dose response relationship:
1
Justification:
As the starting point for the DNEL calculation is a NOAEL according to ECHA Guidance (November 2012), R.8.4.3.1 the default assessment factor for dose response relationship is 1.
AF for differences in duration of exposure:
6
Justification:
Difference in the experimental exposure duration (= subacute) and the duration of exposure for the population and scenario under consideration (= chronic) according to ECHA Guidance (November 2012) Chapter R. 8. Table R.8-5.
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA Guidance (November 2012) R.8, Table R.8-3 the allometric scaling factor for the rat when compared with humans is 4
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 for remaining interspecies differences is suggested in the Guidance Document R.8 (ECHA, 2012)
AF for intraspecies differences:
10
Justification:
According to ECHA Guidance (November 2012) Chapter R.8.4.3.1 the default AF to be applied for intraspecies differences in the general population is 10.
AF for the quality of the whole database:
1
Justification:
Default assessment factor for good/standard quality of database as suggested by the Guidance Document R8 (ECHA, 2012).
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral 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):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Oral data from the rat are used to decide on a corresponding oral dose for humans. Therefore a route-to-route extrapolation is not necessary.
AF for dose response relationship:
1
Justification:
As the starting point for the DNEL calculation is a NOAEL according to ECHA Guidance (November 2012), R.8.4.3.1 the default assessment factor for dose response relationship is 1.
AF for differences in duration of exposure:
6
Justification:
Difference in the experimental exposure duration (= subacute) and the duration of exposure for the population and scenario under consideration (= chronic) according to ECHA Guidance (November 2012) Chapter R. 8. Table R.8-5.
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA Guidance (November 2012) R.8, Table R.8-3 the allometric scaling factor for the rat when compared with humans is 4
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 for remaining interspecies differences is suggested in the Guidance Document R.8 (ECHA, 2012)
AF for intraspecies differences:
10
Justification:
According to ECHA Guidance (November 2012) Chapter R.8.4.3.1 the default AF to be applied for intraspecies differences in the general population is 10.
AF for the quality of the whole database:
1
Justification:
Default assessment factor for good/standard quality of database as suggested by the Guidance Document R8 (ECHA, 2012).
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