Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.8 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):
75
Modified dose descriptor starting point:
NOAEC
DNEL value:
882 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of an inhalation study, a corrected inhalation starting point is derived based on the oral NOAEL of 1000 mg/kg bw/d. The oral NOAEL is corrected for breathing rate (/0.38) and activity (*0.67), resulting in a corrected inhalation NOAEC of 882 mg/m3.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not required: already considered
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value (workers)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
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:
3.3 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):
300
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A study of repeated dose dermal toxicity is not available. Dermal absorption and oral absorption are assumed (worst case) to be equivalent). A corrected dermal NOAEL of 1000 mg/kg bw/d is therefore derived.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
starting point derived from a rat study
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value (workers)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
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

DNEL Derivation

Di-penta is of low acute toxicity, is not an irritant or sensitiser. An OECD 422 screening study with di-penta reports no effects at the highest (limit) dose level tested of 1000 mg/kg bw/d. A study of developmental toxicity performed with di-penta with also reports maternal and developmental NOAELs of 1000 mg/kg bw/d. An overall NOAEL of 1000 mg/kg bw/d is therefore used as a PoD for DNEL derivation.

Inhalation DNELs

Systemic inhalation DNELs

In the absence of an inhalation study, a corrected inhalation starting point is derived from the oral NOAEL of 1000 mg/kg bw/d. The oral NOAEL is corrected for breathing rate (/0.38) and activity (*0.67), resulting in a corrected inhalation NOAEC of 882 mg/m3.

Applying individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 1 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 75. Applying the overall assessment factor to the corrected starting point results in a DNEL of 11.8 mg/m3.

The substance is of very low acute toxicity. No hazard is identified; a short-term systemic inhalation DNEL is not required.

Local inhalation DNELs

The substance is not classified as a skin or eye irritant and there is no evidence for respiratory irritation or sensitisation. In the absence of an identified hazard, a local inhalation DNEL is not derived.

Dermal DNELs

Systemic dermal DNELs

A study of repeated dose dermal toxicity is not available. Dermal absorption and oral absorption are assumed (worst case) to be equivalent). A corrected dermal NOAEL of 1000 mg/kg bw/d is therefore derived. Applying individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 300. Applying the overall assessment factor to the corrected starting point results in a DNEL of 3.3 mg/kg bw/d.

The substance is of very low acute toxicity. No hazard is identified; a short-term systemic dermal DNEL is not required.

Local dermal DNELs

The substance is not classified as a skin or eye irritant and there is no evidence for skin irritation or sensitisation. In the absence of an identified hazard, a local dermal DNEL is not derived.

Di-penta is not classified as an eye irritant.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.9 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):
150
Modified dose descriptor starting point:
NOAEC
DNEL value:
435 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of an inhalation study, a corrected inhalation starting point is derived from the oral NOAEL of 1000 mg/kg bw/d. The oral NOAEL is corrected for breathing rate (/1.15), resulting in a corrected inhalation NOAEC of 435 mg/m3.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
extrapolation from sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not required (already accounted for)
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
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:
1.7 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A study of repeated dose dermal toxicity is not available. Dermal absorption and oral absorption are assumed (worst case) to be equivalent). A corrected dermal NOAEL of 100 mg/kg bw/d is therefore derived.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
extrapolation from a sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
starting point derived from a rat study
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
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:
1.7 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The starting point is derived from an oral study; correction is therefore not required.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
6
Justification:
extrapolation from a sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
starting point derived from a rat study
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
default value
AF for remaining uncertainties:
1
Justification:
default value
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

DNEL Derivation

Di-penta is of low acute toxicity, is not an irritant or sensitiser. A 28-day study with penta reports no effects at the single dose level tested of 1000 mg/kg bw/d. A study of developmental toxicity performed penta with also reports maternal and developmental NOAELs of 1000 mg/kg bw/d. A reproductive toxicity screening study with penta reports a NOEL of 100 mg/kg bw/d, based on increased incidences of diarrhoea / soft stool at dose levels of 300 and 1000 mg/kg bw/d; slightly increased water consumption was observed at the highest dose level of 1000 mg/kg bw/d. Findings are considered to reflect incomplete gastrointestinal absorption and are not of relevance to the worker risk assessment. An overall NOAEL of 1000 mg/kg bw/d is therefore used as a PoD for DNEL derivation.

Inhalation DNELs

Systemic inhalation DNELs

In the absence of an inhalation study, a corrected inhalation starting point is derived from the oral NOAEL of 1000 mg/kg bw/d. The oral NOAEL is corrected for breathing rate (/1.15), resulting in a corrected inhalation NOAEC of 435 mg/m3.

Applying individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 1 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 150. Applying the overall assessment factor to the corrected starting point results in a DNEL of 2.9 mg/m3.

The substance is of very low acute toxicity. No hazard is identified; a short-term systemic inhalation DNEL is not required.

Local inhalation DNELs

The substance is not classified as a skin or eye irritant and there is no evidence for respiratory irritation or sensitisation. In the absence of an identified hazard, a local inhalation DNEL is not derived.

Dermal DNELs

Systemic dermal DNELs

A study of repeated dose dermal toxicity is not available. Dermal absorption and oral absorption are assumed (worst case) to be equivalent). A corrected dermal NOAEL of 1000 mg/kg bw/d is therefore derived.

Applying individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 600. Applying the overall assessment factor to the corrected starting point results in a DNEL of 1.7 mg/kg bw/d.

The substance is of very low acute toxicity. No hazard is identified; a short-term systemic dermal DNEL is not required.

Local dermal DNELs

The substance is not classified as a skin or eye irritant and there is no evidence for skin irritation or sensitisation. In the absence of an identified hazard, a local dermal DNEL is not derived.

Oral DNELs

Systemic oral DNELs

The starting point is derived from an oral study; correction is therefore not required.

Applying individual assessment factors of 1 (for dose-response relationship), 6 (for duration of exposure), 4 (for allometric scaling), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) results in an overall assessment factor of 600. Applying the overall assessment factor to the corrected starting point results in a DNEL of 1.7 mg/kg bw/d.

The substance is of very low acute toxicity. No hazard is identified; a short-term systemic oral DNEL is not required.

 

The substance is not classified as an eye irritant.