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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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