4-hydroxymethyl-1,3-dioxolan-2-one

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

41.75 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

other: according to ECETOC Technical Report #86.

Overall assessment factor (AF):

3

Dose descriptor:

other: NOAEC: 125.25 mg/m³

AF for dose response relationship:

1

AF for differences in duration of exposure:

1

Justification:

Since the most sensitive endpoint was based on an adaptive response and glycerol is not expected to accumulate, a duration adjustment to chronic exposure was not used.

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for local effects

AF for other interspecies differences:

1

AF for intraspecies differences:

3

Justification:

according to ECETOC Technical Report #86.

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Most sensitive endpoint:

acute toxicity

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Acute / short-term exposure (systemic and local effects):
- An acute dermal toxicity test was performed in rabbits. None of the rabbits died at 3000 mg/kg, the highest dose level tested. The LD50 is greater than 3000 mg/kg bw/day. Therefore, a DNEL for acute dermal toxicity is not quantifiable.
- An acute inhalation toxicity test was performed in rats. None of the rats died at 5.6 mg/L, the only dose tested. The LC50 value was greater than 5.6 mg/L. Therefore, a DNEL or acute inhalation toxicity is not quantifiable.
- Based on the available data and according to the criteria laid down in the DSD and CLP Regulation (EC) 1272/2008, glycerine carbonate is neither classified for skin irritation/corrosion nor for eye damage. No DNEL was derived based on the available data.

 

Long-term exposure (systemic effects):

- Dermal: No-threshold effect and/or no dose-response information available for systemic effects neither from glycerine carbonate nor from the read-across substance glycerol. The long-term dermal DNEL was based on no effects in the rabbit dermal subchronic (45 wk) toxicity study. The rat subchronic study identified a NOAEL of 4580 mg/kg, based on cloudy swelling and hypertrophy of liver, but this is considered to be an adaptive response to high-dose administration of a normal component of intermediate metabolism, and of questionable relevance for exposure by the dermal route of exposure.

- Inhalation: No-threshold effect and/or no dose-response information available for systemic effects neither from glycerine carbonate nor from the read-across substance glycerol.

 

Long-term exposure (local effects):

- Inhalation: No long term toxicity studies via the inhalation route are available for glycerine carbonate. However, a systemic inhalation NOAEC of 167 mg/m³ was obtained for the read-across substance glycerol in a 90 day repeated dose toxicity study in rats. A conversion factor of 0.75 was used to convert from 6 to 8 hours of exposure per day. Therefore, the dose descriptor starting point = 125.25 mg/m³ (167 mg/m³ x (6 hours/8 hours)).

With an overall assessment factor of 3 (intraspecies differences according to ECETOC Technical Report #86.), the long-term DNEL, inhalation for local effects of 125.25 mg/m³/3 = 41.75 mg/m³ is derived.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.35 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

other: according to ECETOC Technical Report #86.

Overall assessment factor (AF):

5

Dose descriptor:

other: NOAEC 41.75 mg/m³

AF for dose response relationship:

1

AF for differences in duration of exposure:

1

Justification:

Since the most sensitive endpoint was based on an adaptive response and glycerol is not expected to accumulate, a duration adjustment to chronic exposure was not used.

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for local effects

AF for other interspecies differences:

1

AF for intraspecies differences:

5

Justification:

according to ECETOC Technical Report #86.

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Most sensitive endpoint:

acute toxicity

DNEL related information

Local effects

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Most sensitive endpoint:

acute toxicity

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

229 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: according to ECETOC Technical Report #86.

Overall assessment factor (AF):

20

Modified dose descriptor starting point:

NOAEL

Value:

4 580 mg/kg bw/day

AF for dose response relationship:

1

AF for differences in duration of exposure:

1

AF for interspecies differences (allometric scaling):

4

Justification:

Rats to humans

AF for other interspecies differences:

1

Justification:

according to ECETOC Technical Report #86.

AF for intraspecies differences:

5

Justification:

according to ECETOC Technical Report #86.

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

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

- An acute dermal toxicity test was performed in rabbits. None of the rabbits died at 3000 mg/kg, the highest dose level tested. The LD50 is greater than 3000 mg/kg bw/day. Therefore, a DNEL for acute dermal toxicity is not quantifiable. 

- An acute oral toxicity test was performed in rats. The LD50 was determined to be greater than 5000 mg/kg bw/day. No acute DNEL was derived based on the available data.

- An acute inhalation toxicity test was performed in rats. None of the rats died at 5.6 mg/L, the only dose tested. The LC50 value was greater than 5.6 mg/L. Therefore, a DNEL or acute inhalation toxicity is not quantifiable.

- Based on the available data and according to the criteria laid down in the DSD and CLP Regulation (EC) 1272/2008, glycerine carbonate is neither classified for skin irritation/corrosion nor for eye damage. No DNEL was derived based on the available data.

 

Long-term exposure (systemic effects): 

- Dermal: No-threshold effect and/or no dose-response information available for systemic effects neither from glycerine carbonate nor from the read-across substance glycerol. The long-term dermal DNEL was based on no effects in the rabbit dermal subchronic (45 wk) toxicity study. The rat subchronic study identified a NOAEL of 4580 mg/kg, based on cloudy swelling and hypertrophy of liver, but this is considered to be an adaptive response to high-dose administration of a normal component of intermediate metabolism, and of questionable relevance for exposure by the dermal route of exposure.

- Inhalation: No-threshold effect and/or no dose-response information available for systemic effects neither from glycerine carbonate nor from the read-across substance glycerol.

- Oral: The long-term oral DNEL was based upon on cloudy swelling and hypertrophy of liver in the rat subchronic study (NOAEL 4580 mg/kg), which is considered to be an adaptive response to high-dose administration of a normal component of intermediate metabolism. There were no effects on tumour response or inflammation in a chronic bioassay. With an overall assessment factor of 20 (x4 for interspecies differences and x5 for intraspecies differences), the long-term DNEL, inhalation for systemic effects of 4580 mg/kg/20 = 242 mg/kg is derived.

 

Long-term exposure (local effects):

- No long term toxicity studies via the inhalation route are available for glycerine carbonate. However, a systemic inhalation NOAEC of 167 mg/m³ was obtained for glycerol in a 90 day repeated dose study on rats. A conversion factor of 0.25 was used to convert from 6 to 24 hours of exposure per day. Therefore, the dose descriptor starting point =41.75 mg/m³ (167 mg/m³ x (6 hours/24 hours)).

With an overall assessment factor of 5 (intraspecies differences), the long-term DNEL, inhalation for systemic effects of 41.75 mg/m³/5 = 8.35 mg/m³ is derived.