Registration Dossier

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.35 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):
10
Modified dose descriptor starting point:
NOAEC
Value:
3.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
Esters are not susceptible to acid catalysed hydrolysis in the stomach, but to esterase activity in the plasma. The target organ is the liver.
AF for dose response relationship:
1
Justification:
A NOEL is available.
AF for differences in duration of exposure:
2
Justification:
A 90-day study in rats is available.
AF for interspecies differences (allometric scaling):
1
Justification:
included in modification of the dose descriptor starting point
AF for other interspecies differences:
1
Justification:
Liver identified as target organ in rabbits and rats. Value in rats due to peroxisome proliferation used to derive NOEL.
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
Various mechanistic studies available.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
0.5 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
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A factor of 0.1 is included to account for the high molecular weight and the high log Pow of the components.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic study
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
Justification:
Liver identified as target organ in rabbits and rats. Value in rats due to peroxisome proliferation used to derive NOEL.
AF for intraspecies differences:
5
Justification:
worker
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
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

A 28 d and a 90 d repeated dose oral toxicity study as well as studies on toxicity to reproduction with rats and rabbits with the test substance are available. The liver was identified as the target organ. A NOAEL of 2 mg/kg bw was identified as the NOAEL for subchronic exposure. The substance is a potent peroxisome proliferator in rats. It is not genotoxic.

For effects observed in the reproductive toxicity studies, the same or higher NOELs were established. The relevant period was covered, so no correction factor for study duration is needed for these endpoints. The DNEL derived from the repeated dose toxicity is lowest and gives adequate safety for the other endpoints.

In order to adjust for inhalation, modifications have to be made for workers. Factors were applied to adjust for human respiratory conditions as well as duration of exposure. An assessment factor of 1 was used for differences in absorption between oral and inhalative route. Further conversion factors were used as advised in the ECHA-guidance Chapter R. 8: Conversion of oral dose to corresponding air concentration: 1/0.38; Correction for respiratory volume under light activity: 6.7/10.

Corrected starting point (worker): 2 mg/kg bw/day x 1/0.38 m3/kg bw/d x 6.7 m3 (8h)/10 m3 (8h) = 3.5 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.085 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:
1.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
see worker
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
1
Justification:
included in modification of the dose descriptor starting point
AF for other interspecies differences:
10
AF for intraspecies differences:
1
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:
hazard unknown (no further information necessary)
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:
0.25 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
Modified dose descriptor starting point:
NOAEL
Value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
see worker
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
10
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:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
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:
0.025 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
Modified dose descriptor starting point:
NOAEL
Value:
2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not needed.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
10
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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

In order to adjust for inhalation, modifications have to be made for the general population. Factors were applied to adjust for human respiratory conditions as well as duration of exposure. An assessment factor of 1 was used for differences in absorption between oral and inhalative route. Further conversion factors were used as advised in the ECHA-guidance Chapter R. 8: Conversion of oral dose to corresponding air concentration: 1/0.38; Correction for respiratory volume under light activity: 6.7/10.

Corrected starting point (general population): 2 mg/kg bow/day x 1/1.15 m3/kg bw/d = 1.7 mg/m3

Categories Display