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:
1 556 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Modified dose descriptor starting point:
NOAEC
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:
65 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
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

Additional information - workers

No DNELs for acute exposure have been derived for dipropylene glycol methyl ether acetate as this substance is not classified for acute toxicity by any route and no acute effects have been observed in the repeated exposure studies.

Dipropylene glycol methyl ether acetate did not show any adverse effects regarding sensitization, mutagenicity or reproductive toxicity. Therefore, no DNELs have been derived for these endpoints.

No DNELs have been derived for local effects as no such effects were observed in any of the repeated dose studies. Therefore, the DNELs for systemic effects are considered to be sufficiently protective for potential local effects.

Worker-DNEL long-term for inhalation route

Based on toxicokinetics data summarized in section 5.1.3 (IUCLID chapter 7.1.1), dipropylene glycol methyl ether acetate is expected to be rapidly hydrolyzed to yield dipropylene glycol methyl ether. Thus, it is appropriate to conclude that the acetate behaves in a similar way to the parent ether due to the rapid conversion. Therefore, data on dipropylene glycol methyl ether are used to support the dataset for dipropylene glycol methyl ether acetate.

The relevant dose-descriptor for long-term exposure via the inhalation route is the NOAEL of > 200 ppm (or mg/kg bw/d) from the 13-week inhalation toxicity study with dipropylene glycol methyl ether in rats. For the DNEL calculation we have deviated from the default approach as prescribed in the ECHA guidance documents, for the following reasons. The EU Scientific Committee for Occupational Exposure Limits (SCOEL) and the German MAK Commission have established a workplace exposure level of 50 ppm for dipropylene glycol methyl ether. Based on analogy with the toxicological profile of dipropylene glycol methyl ether and the toxicokinetic behaviour of dipropylene glycol methyl ether acetate (rapid hydrolysis in the blood to dipropylene glycol methyl ether), 50 ppm is used as the Worker-DNEL-long term for the inhalation route for dipropylene glycol methyl ether acetate.

Worker-DNEL long-term for dermal route

No repeated dose study with dermal exposure is available for dipropylene glycol methyl ether acetate. The 13-week inhalation study conducted with dipropylene glycol methyl etherwas selected as the most relevant study for determining the DNEL because of the relevance of the route for repeated exposure.The relevant dose-descriptor for long-term exposure via the dermal route is the worker-DNEL of 50 ppm established for dipropylene glycol methyl ether by the SCOEL and the German MAK Commission based on the 13-week inhalation toxicity studies in rats and rabbits. The dose descriptor has been converted into a dermal dose of 65 mg/kg bw/day according to the guidance document (ECHA, Chapter R.8). No additional assessment factors have been applied for inter- and intra-species differences as the starting point was the worker-DNEL for inhalation exposure.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
46 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
2
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:
15 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
2
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:
1.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

General population-DNEL long-term for inhalation route

For the DNEL calculation we have deviated from default approach as described in the ECHA guidance documents, for the reasons mentioned above. The dose descriptor used was the worker-DNEL-long term for the inhalation route which was corrected for the differences in duration of exposure between worker and consumer (24h per day, 7 days per week) and the intra-species difference.

General population-DNEL long-term for dermal route

No repeated dose study with dermal exposure is available for dipropylene glycol methyl ether acetate. The 13-week inhalation study was selected as the most relevant study for determining the DNEL because of the relevance of the route for repeated exposure.The relevant dose-descriptor for long-term exposure via the dermal route is the worker-DNEL of 50 ppm based on the 13-week inhalation toxicity studies in rats and rabbits. The dose descriptor was corrected for exposure conditions - according to the guidance document - as the test material was administered 5 days per week. No correction for inter-species differences was done as the starting point was the worker-DNEL for inhalation exposure. To correct for intra-species differences and for differences in the duration of exposure (sub-chronic to chronic) the default assessment factors as specified in the guidance document (Chapter R.8) have been used to calculate the DNEL.


General population-DNEL long-term for oral route

The relevant dose-descriptor for long-term exposure via the oral route is the NOAEL of 1000 mg/kg bw/day from a 28-day oral gavage study in rats. A correction of the dose descriptor for exposure conditions is not needed as the test material was administered 7 days per week. To correct for inter- and intra-species differences and for differences in the duration of exposure (sub-chronic to chronic) the default assessment factors as specified in the guidance document (Chapter R.8) have been used to calculate the DNEL.