Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.36 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
101.95 mg/m³
Explanation for the modification of the dose descriptor starting point:
As no long-term study on inhalation is available, route-to-route extrapolation has been performed (oral to inhalation).
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Extrapolation of exposure duration from subacute to chronic exposure
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for rats
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
2.5 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):
100
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Extrapolation of exposure duration from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
default assessment factor for rats
AF for other interspecies differences:
2.5
Justification:
default assessment factor for rats
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
medium hazard (no threshold derived)

Additional information - workers

Acute/short-term exposure (systemic and local effects)

POPDA is classified as a category 1C skin irritant and a category 1 eye irritant. Short-term peak exposures are not expected, and therefore, the long-term dermal DNELs for both systemic and local effects are expected to be adequately protective of any short-term exposures.

 

Long-term exposure (systemic effects)

- Inhalation: No long-term inhalation toxicity studies are available for POPDA. However, data from an oral PND toxicity study could be used after extrapolation to the inhalation route. POPDA was administered orally to rabbits for 22 days (day 6 to 28 after mating) at doses of 0, 15,50, and 115 mg/kg. The NOAEL for systemic effects was deemed to be 50 mg/kg based on inappetance, reduced body weight, effects on food consumption and a single mortality.

For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 50 mg/kg bw/day x 1/(0.23 m³/kg/day) x 6.7 m³/10m³ x 7/5 x 0.5 = 101.95 mg/m³. The oral dose for rabbits was converted to the corresponding air concentration using a standard breathing volume for the rabbit (0.23 m³/kg for 8 hours exposure of workers). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhalation volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). a correction is made for days of exposure: 7 for rabbits during the study, 5 working days for worker population. In addition, the NOAEL need to be divided by 2 as the bioavailability via the inhalation route is considered as 100%, while for oral exposure this is only 50%. With an overall assessment factor of 75: 6 (difference in duration subacute to chronic) x 5 (intraspecies differences) x 2.5 (interspecies - remaining differences), the long-term DNEL, inhalation for systemic effects of 101.95 mg/m³/75 = 1.36 mg/m³ is derived.

- Dermal: The long-term systemic DNEL for the dermal route was derived based on the 90 days dermal repeated dose toxicity test. With an overall assessment factor of 100: 2 (difference in duration subchronic to chronic) x 4 (interspecies differences) x 2.5 (remaining differences) x 5 (intraspecies differences), the long-term DNEL, dermal for systemic effects of 250/100 = 2.5 mg/kg/day is derived.

Long-term exposure (local effects)

POPDA is classified as skin corrosive substance category 1C according to the CLP Regulation (EC) No. 1272/2008. The skin and eye irritation tests (similar to OECD Guideline 404 and 405) are indicate a corrosive potential. The tests do not provide dose-response data that could be used for the derivation of a DNEL. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee adequately control of risks", it is necessary to stipulate risk management measures that prevent skin and eye exposure.

Hazard for the eyes - Local effects

Based on the available data and according to the criteria laid down in the CLP Regulation (EC) 1272/2008, POPDA is classified as Eye damage category 1 (moderate hazard) and Skin corrosion category 1C (moderate hazard). No dose response curve can be derived based on the available data and so only an indication of the medium hazard category can be given. The hazard categories are indicated in the Guidance on Information Requirements and Chemical Safety Assessment - Part E Risk Characterisation.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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

No effect threshold levels derived for general population, as no consumer use is expected.