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EC number: 246-770-3 | CAS number: 25265-71-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 238 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 3
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 712 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Based on drinking water study. Starting point is NOAEL of 470mg/kg/day. Oral absorption factor 86%, inhalation assumed 100%. Extrapolation assumes rat inhalation rate of 0.38m3/kgbw/8hr corrected for activity driven volume of 6.7/10. See discussion.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1
- Justification:
- Chronic study
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Not required for inhalation
- AF for other interspecies differences:
- 1
- Justification:
- See discussion
- AF for intraspecies differences:
- 3
- Justification:
- See discussion
- 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:
- 84 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 12
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 010 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Based on drinking water study. Starting point is NOAEL of 470mg/kg/day. Oral absorption factor 86%, dermal 40%.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1
- Justification:
- Sub chronic study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human
- AF for other interspecies differences:
- 1
- Justification:
- see discussion
- AF for intraspecies differences:
- 3
- Justification:
- see discussion
- 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:
- no hazard identified
Additional information - workers
According to the REACH guidance on information requirements and chemical safety assessment a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.
The available toxicokinetic study on the structural analogue of dipropylene glycol, tripropylene glycol, indicated a recovery of at least 86% of the total dose administered orally. Based on this, the oral absorption percentage used for DNEL derivation (in case of route-to-route extrapolation) is set to 86%. As no data are available on inhalation absorption, the default value of 100%, as set in Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, will be used for DNEL derivation in case of route-to-route extrapolation.
Regarding dermal absorption, an available in vitro study on dipropylene glycol indicated 0.075% dermal absorption, using an infinite exposure conditions. Based on expert judgment, a value of 40% for dermal absorption has been chosen to be used in the risk assessment and DNEL derivation. This value has been chosen as an average value between the percentage of dermal absorption obtained in the study and the maximal oral absorption (corresponding to 86%), and is considered to represent a worst-case approach.
Acute toxicity
Dipropylene glycol is not classified for acute toxicity and therefore derivation of a DNELacute is not necessary.
Dipropylene glycol is not irritating to the skin, eyes and respiratory tract and not sensitising to the skin. Therefore, no DNELs are derived for these endpoints.
Long-term toxicity
Regarding repeated dose toxicity, the lowest NOAEL was established in the 2-year drinking water study with rats (National Toxicology Program, 2004) and amounted to 470 mg/kg bw/day for male and 530 mg/kg bw/day for female rats (actual ingested doses, corresponding to10000 ppm in drinking water), based on the effects in liver (bile duct hyperplasia) and nasal cavity (increased incidence of olfactory epithelial atrophy and/or degeneration). The lowest of these values shall be used for risk assessment and DNEL derivation for systemic effects by long-term exposure.
No inhalation and dermal long-term exposure studies with dipropylene glycol were available for assessment.
Dipropylene glycol is assessed to be non-mutagenic and not carcinogenic. Based on this, no separate risk characterisation for mutagenicity and carcinogenicity is needed.
Dipropylene glycol did not cause effects on development or fertility. Two guideline developmental toxicity studies were executed with dipropylene glycol, one in rats and one in rabbits. In neither of these studies developmental effects were observed up to the highest dose tested (5000 mg/kg bw/d for rats, 1200 mg/kg bw/day for rabbits). These doses are much higher than the established NOAEL for repeated dose toxicity (470 mg/kg bw/d (see above)). In the rat study, maternal toxicity was observed at doses of 2000 and 5000 mg/kg bw/d (NOAEL 800 mg/kg bw/d), consisting of clinical signs of toxicity (ataxia, weight loss, lethargy, unstable gait, piloerection, morbidity) and/or mortality and increased relative liver weight. No reproductive toxicity studies were available for dipropylene glycol; however, a continuous breeding study with mice, comparable to OECD 416 two-generation study, was available for a structural analogue, monopropylene glycol. In this study a NOAEL of 10100 mg/kg bw/day (highest dose tested) was observed for effects on fertility.
As no studies using dermal or inhalation route of exposure were available, a route-to-route extrapolation shall be used to derive DNELs for these exposure routes.
DNEL calculation
The DNELs are derived using the scientifically based assessment factors as reported by ECETOC (ECETOC (2003). Derivation of assessment factors for human health risk assessment. Technical Report # 86, ISSN-0773-6347-86, Brussels, Belgium).
Long term – inhalation, systemic effects
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 470 mg/kg bw/day |
Based on effects on liver and nose in a 2-year drinking water study with rats |
Step 2) Modification of starting point |
0.86
1
0.38 m3/kg bw
6.7 m3/10 m3 |
Proportion of the oral absorption, based on the available toxicokinetics study with tripropylene glycol;
Proportion inhalation absorption (default value, as proposed in the REACH guidance (R.8.4.2)
Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance (R.8.4.2)
Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3). |
Step 3) Assessment factors |
|
|
Interspecies |
1 |
No allometric scaling is necessary in case of inhalation exposure |
Intraspecies |
3 |
The default assessment factor for workers, as proposed in the ECETOC guidance |
Exposure duration |
1 |
As the NOAEL is obtained in a chronic study, no correction for exposure duration is necessary |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
470 x (0.86/1) x (6.7/10) / (0.38 x 1 x 3 x 1 x 1 x 1) = 238 mg/m3 |
Long term – dermal, systemic effects
Description |
Value |
Remark |
|
Step 1) Relevant dose-descriptor |
NOAEL: 470 mg/kg bw/day |
Based on effects on liver and nose in a 2-year drinking water study with rats |
|
Step 2) Modification of starting point |
0.86
0.40
|
Proportion of the oral absorption, based on the available toxicokinetics study with tripropylene glycol; Proportion dermal absorption (reasonable worst case for oral-to-dermal extrapolation) |
|
Step 3) Assessment factors |
|
|
|
Interspecies |
4 |
Allometric scaling factor for rat |
|
Intraspecies |
3 |
The default assessment factor for workers, as proposed in the ECETOC guidance |
|
Exposure duration |
1 |
As the NOAEL is obtained in a chronic study, no correction for exposure duration is necessary |
|
Dose response |
1 |
|
|
Quality of database |
1 |
|
|
DNEL |
Value |
||
|
470 x (0.86/0.40) / (4 x 3 x 1 x 1 x 1) = 84 mg/kg bw/day |
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 70 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 5
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 351 mg/m³
- Explanation for the modification of the dose descriptor starting point:
- Based on drinking water study. Starting point is NOAEL of 470mg/kg/day. Oral absorption factor 86%, inhalation assumed 100%. Extrapolation assumes rat inhalation rate of 1.15m3/kgbw/24hr. See discussion.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1
- Justification:
- Chronic study
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Not required for inhalation
- AF for other interspecies differences:
- 1
- Justification:
- see discussion
- AF for intraspecies differences:
- 5
- Justification:
- see discussion
- 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
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 51 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 20
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 1 010 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
- Based on drinking water study. Starting point is NOAEL of 470mg/kg/day. Oral absorption factor 86%, dermal 40%.
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1
- Justification:
- Chronic study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human
- AF for other interspecies differences:
- 1
- Justification:
- see discussion
- AF for intraspecies differences:
- 5
- Justification:
- see discussion
- 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
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 24 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 20
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 470 mg/kg bw/day
- AF for dose response relationship:
- 1
- AF for differences in duration of exposure:
- 1
- Justification:
- chronic study
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- rat to human
- AF for other interspecies differences:
- 1
- Justification:
- see discussion
- AF for intraspecies differences:
- 5
- Justification:
- see discussion
- 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
According to the REACH guidance on information requirements and chemical safety assessment a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.
The available toxicokinetic study on the structural analogue of dipropylene glycol, tripropylene glycol, indicated a recovery of at least 86% of the total dose administered orally. Based on this, the oral absorption percentage used for DNEL derivation (in case of route-to-route extrapolation) is set to 86%. As no data are available on inhalation absorption, the default value of 100%, as set in Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, will be used for DNEL derivation in case of route-to-route extrapolation.
Regarding dermal absorption, an available in vitro study on dipropylene glycol indicated 0.075% dermal absorption, using an infinite exposure conditions.Based on expert judgment, a value of 40% for dermal absorption has been chosen to be used in the risk assessment and DNEL derivation. This value has been chosen as an average value between the percentage of dermal absorption obtained in the study and the maximal oral absorption (corresponding to 86%), and is considered to represent a worst-case approach.
Acute toxicity
Dipropylene glycol is not classified for acute toxicity and therefore derivation of a DNELacute is not necessary.
Dipropylene glycol is not irritating to the skin, eyes and respiratory tract and not sensitising to the skin. Therefore, no DNELs are derived for these endpoints.
Long-term toxicity
Regarding repeated dose toxicity, the lowest NOAEL was established in the 2-year drinking water study with rats (National Toxicology Program, 2004) and amounted to 470 mg/kg bw/day for male and 530 mg/kg bw/day for female rats (actual ingested doses, corresponding to10000 ppm in drinking water), based on the effects in liver (bile duct hyperplasia) and nasal cavity(increased incidence of olfactory epithelial atrophy and/or degeneration). The lowest of these values shall be used for risk assessment and DNEL derivation for systemic effects by long-term exposure.
No inhalation and dermal long-term exposure studies with dipropylene glycol were available for assessment.
Dipropylene glycol is assessed to be non-mutagenic and not carcinogenic. Based on this, no separate risk characterisation for mutagenicity and carcinogenicity is needed.
Dipropylene glycol did not cause effects on development or fertility. Two guideline developmental toxicity studies were executed with dipropylene glycol, one in rats and one in rabbits. In neither of these studies developmental effects were observed up to the highest dose tested (5000 mg/kg bw/d for rats, 1200 mg/kg bw/day for rabbits). These doses are much higher than the established NOAEL for repeated dose toxicity (470 mg/kg bw/d (see above)). In the rat study, maternal toxicity was observed at doses of 2000 and 5000 mg/kg bw/d (NOAEL 800 mg/kg bw/d), consisting of clinical signs of toxicity (ataxia, weight loss, lethargy, unstable gait, piloerection, morbidity) and/or mortalityand increased relative liver weight. No reproductive toxicity studies were available for dipropylene glycol; however, a continuous breeding study with mice, comparable to OECD 416 two-generation study, was available for a structural analogue, monopropylene glycol. In this study a NOAEL of 10100 mg/kg bw/day (highest dose tested) was observed for effects on fertility.
As no studies using dermal or inhalation route of exposure were available, a route-to-route extrapolation shall be used to derive DNELs for these exposure routes.
DNEL calculation
The DNELs are derived using the scientifically based assessment factors as reported by ECETOC (ECETOC (2003). Derivation of assessment factors for human health risk assessment. Technical Report # 86, ISSN-0773-6347-86, Brussels, Belgium).
Long term - inhalation, systemic effects
Description |
Value |
Remark |
Step 1) Relevant dose-descriptor |
NOAEL: 470 mg/kg bw/day |
Based on effects on liver and nose in a 2-year drinking water study with rats |
Step 2) Modification of starting point |
0.86
1
1.15 m3/kg bw
|
Proportion of the oral absorption, based on the available toxicokinetics study with tripropylene glycol;
Proportion inhalation absorption (default value, as proposed in the REACH guidance (R.8.4.2)
Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance (R.8.4.2)
|
Step 3) Assessment factors |
|
|
Interspecies |
1 |
No allometric scaling is necessary in case of inhalation exposure |
Intraspecies |
5 |
The default assessment factor for general population, as proposed in the ECETOC guidance |
Exposure duration |
1 |
As the NOAEL is obtained in a chronic study, no correction for exposure duration is necessary |
Dose response |
1 |
|
Quality of database |
1 |
|
DNEL |
Value |
|
|
470 x (0.86/1) / (1.15 x 1 x 5 x 1 x 1 x 1) = 70 mg/m3 |
Long term – dermal, systemic effects
Description |
Value |
Remark |
|
Step 1) Relevant dose-descriptor |
NOAEL: 470 mg/kg bw/day |
Based on effects on liver and nose in a 2-year drinking water study with rats |
|
Step 2) Modification of starting point |
0.86
0.40
|
Proportion of the oral absorption, based on the available toxicokinetics study with tripropylene glycol; Proportion dermal absorption (reasonable worst case for oral-to-dermal extrapolation) |
|
Step 3) Assessment factors |
|
|
|
Interspecies |
4 |
Allometric scaling factor for rat |
|
Intraspecies |
5 |
The default assessment factor for general population, as proposed in the ECETOC guidance |
|
Exposure duration |
1 |
As the NOAEL is obtained in a chronic study, no correction for exposure duration is necessary |
|
Dose response |
1 |
|
|
Quality of database |
1 |
|
|
DNEL |
Value |
||
|
470 x (0.86/0.40) / (4 x 5 x 1 x 1 x 1) = 51 mg/kg bw/day |
Long term - oral, systemic effects
Description |
Value |
Remark |
|
Step 1) Relevant dose-descriptor |
NOAEL: 470 mg/kg bw/day |
Based on effects on liver and nose in a 2-year drinking water study with rats |
|
Step 2) Modification of starting point |
1
|
No modification of the starting point is necessary |
|
Step 3) Assessment factors |
|
|
|
Interspecies |
4 |
Allometric scaling factor for rat |
|
Intraspecies |
5 |
The default assessment factor for general population, as proposed in the ECETOC Guidance |
|
Exposure duration |
1 |
As the NOAEL is obtained in a chronic study, no correction for exposure duration is necessary |
|
Dose response |
1 |
|
|
Quality of database |
1 |
|
|
DNEL |
Value |
||
|
470 / (4 x 5 x 1 x 1 x 1) = 24 mg/kg bw/day |
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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