Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
59 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
Modified dose descriptor starting point:
NOAEC
Value:
1 182 mg/m³
Explanation for the modification of the dose descriptor starting point:
Conservative factor of 2 has been included in NOAEC to address potential differences in inhalation and oral bioavailability
AF for dose response relationship:
1
Justification:
Clear dose response with minimal toxicological findings up to the highest dose
AF for differences in duration of exposure:
2
Justification:
Based on ECHA Guidance: subchronic to chronic study extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA guidance, route-to-route extrapolation addresses allometic scaling
AF for other interspecies differences:
1
Justification:
substance tested in number of different species
AF for intraspecies differences:
5
Justification:
Based on ECHA Guidance for workers
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
no extra uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: Based on SCOEL (2012) TWA value for DPO
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
other: Based on SCOEL (2012) STEL value for DPO

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route-to-route extrapolation; dermal repeated dose study used to derive dermal DNEL.
AF for dose response relationship:
1
Justification:
Clear dose response with minimal toxicological findings up to the highest dose
AF for differences in duration of exposure:
2
Justification:
Based on ECHA Guidance: subchronic to chronic study extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
based on allometric scaling from rat to human (ECHA guidance)
AF for other interspecies differences:
1
Justification:
substance tested in number of different species
AF for intraspecies differences:
5
Justification:
Based on ECHA Guidance for workers
AF for the quality of the whole database:
1
Justification:
ECHA default
AF for remaining uncertainties:
1
Justification:
no extra uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Chronic, Systemic, Worker Inhalation DNEL

The starting point for the calculation of the systemic, long term exposure DNEL is the NOAEL taken from the 3 month oral study of 301 mg/kg/d. 

The assessment factors used to convert this dose to a worker DNEL were:

Route-to-route - 2 (Based on ECHA guidance)

Worker variability - 5 (Based on ECHA guidance)

Time Extrapolation - 2 (Based on ECHA guidance: subchronic to chronic study extrapolation)

Total Assessment Factor = 20

Chronic, systemic, Worker Dermal DNEL

The starting point for the long-term, systemic Dermal DNEL is the 3-month dermal study NOAEL of 1000 mg/kg bw/day.

The assessment factors for extrapolating to a worker DNEL were:

Allometric scaling - 4 (Based on allometric scaling from rat to human from ECHA guidance)

Worker variability - 5 (Based on ECHA guidance)

Time extrapolation - 2 (Based on ECHA guidance: subchronic to chronic extrapolation)

Total assessment factor = 40

Chronic, Local, Worker Inhalation DNEL

The chronic local inhalation DNEL for workers was set based on SCOEL (2012) value for diphenyl ether based on irritation of the eyes and upper respiratory tract of laboratory animals. 8-hr TWA of 1 ppm or 7 mg/m3 was set for diphenyl ether. This value was used for risk assessment and would be protective against systemic effects occurring at higher exposure levels.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population