Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
123.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
6
Dose descriptor starting point:
NOAEL
Value:
839.6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
739.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

Study with the lowest NOAEL

A worst case default factor for route-to-route extrapolation (oral-to-inhalation) proposed by ECHA is not assigned as a higher absorption via the inhalation route

compared to the oral route is not expected because of the lipophilic properties of the substance. An evaluation of several substances for differences in their oral and inhalation absorption support this assumption [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to Derive DNELs (2009) ].

AF for dose response relationship:
1
Justification:
Default (DNEL generation plugin)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL generation plugin)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL generation plugin)
AF for other interspecies differences:
1
Justification:
An additional factor for "remaining interspecies differences" as proposed by ECHA is scientifically not justified and arbitrary since the allometric scaling factor fully accounts for interspecies differences [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to Derive DNELs (2010), and Publication No. 901 of the Committee for Hazardous Substances (AGS) of the German Federal Institute for Occupational Safety and Health (BAuA) April 2010].
AF for intraspecies differences:
3
Justification:
ECETOC recommends in its Technical report No. 86 ("Derivation of Assessment Factors for Human Health Risk Assessment"; February 2003); and a default assessment factor for intraspecies differences of 3 for workers deviating from the ECHA proposed assessment factor of 5.
AF for the quality of the whole database:
1
Justification:
Default (DNEL generation plugin)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
24
Dose descriptor starting point:
NOAEL
Value:
839.6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
839.6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Study with the lowest NOAEL.

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 R8.4.2)

AF for dose response relationship:
1
Justification:
Default (DNEL generation plugin)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL generation plugin)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL generation plugin)
AF for other interspecies differences:
1
Justification:
justified and arbitrary since the allometric scaling factor fully accounts for interspecies differences [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to
Derive DNELs (2010), and Publication No. 901 of the Committee for Hazardous Substances (AGS) of the German Federal Institute for Occupational Safety and Health (BAuA) April 2010].
AF for intraspecies differences:
3
Justification:
ECETOC recommends in its Technical report No. 86 ("Derivation of Assessment Factors for Human Health Risk Assessment"; February 2003); and a default assessment factor for intraspecies differences of 3 for workers deviating from the ECHA proposed assessment factor of 5.
AF for the quality of the whole database:
1
Justification:
Default (DNEL generation plugin)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
31.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEL
Value:
839.6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
310.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

Study with the lowest NOAEL

A worst case default factor for route-to-route extrapolation (oral-to-inhalation) proposed by ECHA is not assigned as a higher absorption via the inhalation route

compared to the oral route is not expected because of the lipophilic properties of the substance. An evaluation of several substances for differences in their oral and inhalation absorption support this assumption [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to Derive DNELs (2009) ].

AF for dose response relationship:
1
Justification:
Default (DNEL generation plugin)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL generation plugin)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL generation plugin)
AF for other interspecies differences:
1
Justification:
An additional factor for "remaining interspecies differences" as proposed by ECHA is scientifically not justified and arbitrary since the allometric scaling factor fully accounts for interspecies differences [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to Derive DNELs (2010), and Publication No. 901 of the Committee for Hazardous Substances (AGS) of the German Federal Institute for Occupational Safety and Health (BAuA) April 2010].
AF for intraspecies differences:
5
Justification:
ECETOC recommends in its Technical report No. 86 ("Derivation of Assessment Factors for Human Health Risk Assessment"; February 2003) a default assessment factor for intraspecies
differences for the general population of 5 deviating from the ECHA proposed assessment factor of 10.
AF for the quality of the whole database:
1
Justification:
Default (DNEL generation plugin)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
839.6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
839.6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Study with the lowest NOAEL.

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 R8.4.2)

AF for dose response relationship:
1
Justification:
Default (DNEL generation plugin)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL generation plugin)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL generation plugin)
AF for other interspecies differences:
1
Justification:
justified and arbitrary since the allometric scaling factor fully accounts for interspecies differences [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to
Derive DNELs (2010), and Publication No. 901 of the Committee for Hazardous Substances (AGS) of the German Federal Institute for Occupational Safety and Health (BAuA) April 2010].
AF for intraspecies differences:
5
Justification:
ECETOC recommends in its Technical report No. 86 ("Derivation of Assessment Factors for Human Health Risk Assessment"; February 2003) a default assessment
factor for intraspecies differences for the general population of 5 deviating from the ECHA proposed assessment factor of 10.
AF for the quality of the whole database:
1
Justification:
Default (DNEL generation plugin)
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
839.6 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
839.6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Study with the lowest NOAEL

AF for dose response relationship:
1
Justification:
Default (DNEL generation plugin)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL generation plugin)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL generation plugin)
AF for other interspecies differences:
1
Justification:
An additional factor for "remaining interspecies differences" as proposed by ECHA is scientifically not justified and arbitrary since the allometric scaling factor fully accounts for interspecies differences [ECETOC. Technical Report in preparation: Guidance on Assessment Factors to Derive DNELs (2009), and Publication No. 901 of the Committee for Hazardous Substances (AGS) of the German Federal Institute for Occupational Safety and Health (BAuA), April 2010].
AF for intraspecies differences:
5
Justification:
ECETOC recommends in its Technical report No. 86 ("Derivation of Assessment Factors for Human Health Risk Assessment"; February 2003) a default assessment factor for intraspecies
differences for the general population of 5 deviating from the ECHA proposed assessment factor of 10.
AF for the quality of the whole database:
1
Justification:
Default (DNEL generation plugin)
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:
no hazard identified

Additional information - General Population