Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.61 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):
20
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
66.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

Due to lack of repeated dose toxicity data by the inhalation route, a route to route extrapolation was performed. The NOAEL (oral) is converted into a NOAEC (corrected) in accordance to guidance on information requirements and chemical safety assessment, Chapter R.8, ECHA, May 2008. The NOAEL (oral) has to be divided by a factor of 0.38 m3/kg body weight and corrected for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).In addition, a default factor of 2 is applied to account for differences in oral and inhalative absorption properties. The corrected starting point is therefore:

NOAEC (corrected) = 75 mg/kg / 0.38 m3/kg x 0.5 x (6.7 m3/10m3) = 66.1 mg/m3

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is part of the route to route extrapolation
AF for other interspecies differences:
1
Justification:
Data for two species available (rat and dog)
AF for intraspecies differences:
5
Justification:
standard factor for worker
AF for the quality of the whole database:
1
Justification:
Study database valid and acceptable for assessment
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.88 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):
40
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dermal route is typically covered by oral route information in the absence of data for this administration route. Since no data on dermal penetration are available, a worst case approach is used and 100% dermal penetration is assumed.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
extrapolation from rat to human
AF for other interspecies differences:
1
Justification:
Data for two species available (rat and dog)
AF for intraspecies differences:
5
Justification:
standard factor for worker
AF for the quality of the whole database:
1
Justification:
Study database valid and acceptable for assessment
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Identification of relevant dose descriptor

The available repeated dose data showed kidney as the most sensitive organ in rats and liver at the most sensitive organ in dogs. The effects reported were only present at relatively high doses and marginal or not present at lower dose levelsA new OECD 422 study with 10 week pre-treatment in females confirmed the low systemic toxicity profile of Octabenzone. Here, a NOAEL at the limit dose of 1000 mg/kg body weight was reported with no systemic effects. Nevertheless, following a worst case approach with a focus on studies with longer administration, the 90 day studies with rats were chosen as most relevant, since the kidney effects in rats occurred at lower doses compared to the liver effects in dogs. The most relevant NOAEL is therefore 1500 ppm in feed application after 90 day administration with rats, estimated to be 75 mg/kg body weight.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.63 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):
20
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
32.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

Because no inhalation study is available, a route to route extrapolation was performed. The NOAEL (oral) has to be modified into a NOAEC (corrected) in accordance to guidance on information requirements and chemical safety assessment, Chapter R.8, ECHA, May 2008. Here, the NOAEL has to be divided by a factor of 1.15 m3/kg body weight. In addition, a default factor of 2 is applied to account for differences in oral and inhalative absorption properties. The corrected starting point is therefore:

NOAEC (corrected) = 75 mg/kg / 1.15 m3/kg x 0.5 = 32.6 mg/m3

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is part of the route to route extrapolation
AF for other interspecies differences:
1
Justification:
Data for two species available (rat and dog)
AF for intraspecies differences:
10
Justification:
standard factor for the general population
AF for the quality of the whole database:
1
Justification:
Study database valid and acceptable for assessment
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
0.94 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):
80
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The dermal route is typically covered by oral route information in the absence of data for this administration route. Since no data on dermal penetration are available, a worst case approach is used and 100% dermal penetration is assumed.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
extrapolation from rat to humans
AF for other interspecies differences:
1
Justification:
Data for two species available (rat and dog)
AF for intraspecies differences:
10
Justification:
standard factor for the general population
AF for the quality of the whole database:
1
Justification:
Study database valid and acceptable for assessment
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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:
0.94 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):
80
Dose descriptor starting point:
NOAEL
Value:
75 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation required.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
extrapolation from subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
extrapolation from rat to human
AF for other interspecies differences:
1
Justification:
Data for two species available (rat and dog)
AF for intraspecies differences:
10
Justification:
standard factor for the general population
AF for the quality of the whole database:
1
Justification:
Study database valid and acceptable for assessment
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
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