Glycerol

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

other: additional information on occurrence of Glycerol

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Publication on indisputable facts

Key result

Remarks on result:

other: Glycerol is a naturally occurring substance and part of fish organisms

Conclusions:

Glycerol as fatty acid glyceride and as metabolite of fatty acid glycerides is part of (almost) all organisms.

Executive summary:

"Vegetable oils and animal fats contain mostly triglycerides, but are broken down by natural enzymes (lipases) into mono and diglycerides and free fatty acids and glycerol."
"Glycerol is generally obtained from plant and animal sources where it occurs in triglycerides, esters of glycerol with long-chain carboxylic acids."

Glycerol as fatty acid glyceride and as metabolite of these is part of (almost) all organisms.

Reference 2

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Remarks:

QSAR Toolbox Trend analysis

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
QSAR-Toolbox
2. MODEL (incl. version number)
4.4.1
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 56-81-5
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: long-term toxicity to aquatic invertebrates
- Unambiguous algorithm: linear regression from structurally similar substances
- Defined domain of applicability: structural similarity (≥50%), logKow (-0.78 to 1.49),
- Appropriate measures of goodness-of-fit and robustness and predictivity: Please refer to the attached assessment under 'attached justification'

5. APPLICABILITY DOMAIN
Please refer to the attached assessment under 'attached justification'

6. ADEQUACY OF THE RESULT
Please refer to the attached assessment under 'attached justification'

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Software tool(s) used including version: QSAR Toolbox 4.4.1
- Model(s) used: Trendanalysis, linear regression
- Model description: see field 'Attached justification'
- Justification of QSAR prediction: see field 'Attached justification'

GLP compliance:

no

Test organisms (species):

Daphnia magna

Key result

Dose descriptor:

NOEC

Effect conc.:

897 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Remarks on result:

other: Duration of the test is not applicable for in-silico studies; Basis for effect is not applicable for in-silico studies

Validity criteria fulfilled:

not applicable

Conclusions:

The chronic toxicity (NOEC) of Glycerol to Daphnia magna was estimated using Trend analysis of the OECD QSAR Toolbox version 4.4.1. Based on the presented trend analysis and toxicity effect levels of structurally similar substances, the NOEC for long-term exposure of Daphnia magna to glycerol was estimated to be 897 mg/L.

Executive summary:

The chronic toxicity (NOEC) of Glycerol to Daphnia magna was estimated using Trend analysis of the OECD QSAR Toolbox version 4.4.1..The prediction was performed by linear regression with long-term toxicity values from structurally similar substances. The substances were identified by categorization (a) primary grouping for substances belonging to the “Neutral Organics” class of the Aquatic toxicity classification by ECOSAR and (b) subcategorization for substances with a structural similarity of ≥ 50%. The prediction can only be built if experimental values are available for the structural analogues. Three values were identified.

Model equation: NOEC = 2,65 (±1,00) + 0,389 (±1,02) * log Kow, log(1/mol/L)

Active descriptor: log Kow (calculated)

Data usage: Arithmetic mean (average) value*

Statistics of the prediction model:

N = 4; count of data points

R2 = 0,576; coefficient of detemination

R2adj = 0,363; adjusted coefficient of detemination

SSR = 0,423; sum of squared residuals

s = 0,325; sample standard deviation of residuals

F = 2,71; Fisher function

 

Due to the logKow of glycerol (measured -1.75, and estimated - 1.652) which lies below the recommended parametric boundary for the identified substances (-0,78 to 1,49) for the applicability of the prediction the target substance is considered outside the applicability domain. However, because the logKow values of all focused substances is < 3 the substances in general are considered hydrophilic and are thus capable to permeate through lipid bilayers. Hence, their bioavailability is similar. Based on this information the prediction is considered reliable although the target missed the parametric boundary. The molecular weight (92.10 g/mol) is small and comparable to the molecular weight of the source substances and due to the good water solubility of the substance (1000 mg/L) the prediction of the chronic toxicity value by Trend analysis is considered adequate.

 

NOEC Daphnia magna: 897 mg/L

This study is classified as acceptable and is considered sufficient for classification purposes. Based on the predicted value glycerol does not need to be classified with respect to chronic toxicity to fish according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

 

Reference 3

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
EpiSuite™ (The Estimation Programs Interface [EPI] Suite™)
2. MODEL (incl. version number)
ECOSAR v1.11
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES : OCC(O)CO
CAS: 56-81-5
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Aquatic toxicity
- Unambiguous algorithm: please refer to the QMRF attached under 'attached justification'
- Defined domain of applicability: please refer to the QMRF attached under 'attached justification'
- Appropriate measures of goodness-of-fit and robustness and predictivity: please refer to the QMRF attached under 'attached justification'
- Mechanistic interpretation: please refer to the QMRF attached under 'attached justification'

5. APPLICABILITY DOMAIN
- Descriptor domain: logKow, moelcular weight, water solubility
- Structural domain: please refer to the QMRF attached under 'attached justification'
- Mechanistic domain: please refer to the QMRF attached under 'attached justification'
- Similarity with analogues in the training set: please refer to the QMRF attached under 'attached justification'

6. ADEQUACY OF THE RESULT
please refer to the QMRF attached under 'attached justification'

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Software tool(s) used including version: ECOSAR v1.11
- Model(s) used: ECOSAR v1.11
- Model description: see field 'Attached justification'
- Justification of QSAR prediction: see field 'Attached justification'

GLP compliance:

no

Test organisms (species):

Daphnia magna

Total exposure duration:

16 d

Key result

Duration:

16 d

Dose descriptor:

other: Chronic value

Effect conc.:

2 229.923 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

reproduction

Validity criteria fulfilled:

not applicable

Conclusions:

The chronic value for toxicity to Daphnia magna was estimated using EpiSuite™ (The Estimation Programs Interface [EPI] Suite™) software developed by the US Environmental Protection Agency´s Office of Pollution Prevention and Toxics and Syracuse Research Coroperation (SRC) in the QSAR model ECOSAR v1.11. The 16 d-ChV is 2230 mg/L

Executive summary:

The 16-day-chronic toxicity of Glycerol to Daphnia magna was estimated using the EpiSuite™ (The Estimation Programs Interface [EPI] Suite™)software developed by the US Environmental Protection Agency´s Office of Pollution Prevention and Toxics and Syracuse Research Coroperation (SRC).The model used was ECOSAR v1.11.  The model uses the structure-activity relationships (SARs) to predict the aquatic toxicity of chemicals based on their similarity of structure to chemicals for which the aquatic toxicity has been previously measured. Most SAR calculations in the ECOSAR Class Program are based upon the octanol/water partition coefficient (Kow). There are currently 130 chemical classes programmed into ECOSAR. For those 130 classes, there are a total of 440 QSARs based on publicly available experimental data and confidential studies collected under the EPA New Chemicals Program. For each class, a standard EPA New Chemicals Program aquatic toxicity profile will be created using available QSARs and/or alternate SAR approaches and professional judgment. This standard profile typically contains 3 acute values, and 3 chronic values for fish, daphnid, and green algae. In an effort to complete a profile for each class, 173 endpoints have been estimated using alternative approaches such as acute-to-chronic ratios and substitute QSARs based on scientific judgment.

The chronic value for toxicity to Daphnids was calculated as follows for the neutral organics class:

ESTIMATED TOXICITY:

The daphnid ChV values used to develop this SAR were measured and the octanol water partition coefficients (Kow) were calculated using the computer program, KOWWIN (Version 1.67). The SAR equation used to estimate toxicity is:

Log 16-d ChV (mmol/L) = - 0.7469 log Kow + 0.1961

The ChV is in millimoles per liter (mM/L); N = 29 + 1; and the Coefficient of Determination (R2) = 0.8593. To convert the ChV from mM/L to mg/L, multiply by the molecular weight of the compound.

Maximum Kow: 8.0

Maximum MW: 1000

Due to the logKow of glycerol (measured -1.75, and estimated - 1.652) lies beneath the threshold for a valid prediction. The molecular weight (92.10 g/mol) is also in the recommended range for the applicability domain of the model and due to the good water solubility of the substance (1000 mg/L) the prediction of the chronic toxicity value by ECOSAR is considered adequate.

 

ChV 16 d Daphnids: 2229.923 mg/L

This study is classified as acceptable and is considered sufficient for classification purposes. Based on the predicted value glycerol does not need to be classified with respect to chronic toxicity to aquatic invertebrates according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

Reference 4

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Result from a test with a commercial de-icer mixture. Test duration 7 days. Content of Glycerol indirectly derived from COD, content of other (toxic) substances not clear.

Qualifier:

according to guideline

Guideline:

other: US EPA (2002). Short-term Methods for Estimating the Chronic Toxicity of Effluents and Receiving Waters to Freshwater Organisms. EPA-821-R-02-013. 4th ed., Oct. 2002. US EPA (2002b). Methods for Measuring…EPA-821-R-02-012 5th ed.

GLP compliance:

no

Remarks:

Information on long-term toxicity to daphnia was published in literature. There is no information given on GLP. This report is part of a weight-of-evidence approach and all pieces together result in the conclusion. No GLP therefore is sufficient.

Specific details on test material used for the study:

glycerol content of test material 800 g/L according to derivation in "test material information". Other known constituent NaCl. Further unknown constituents suspected.

Analytical monitoring:

no

Vehicle:

no

Details on test solutions:

dilution water: "moderately hard laboratory water":
MgSO4: 60mg/L
NaHCO3: 96 mg/L
KCl: 4mg/L
CaSO4*2H2O: 60mg/L
Na2SeO4: 0.0024mg/L

Test organisms (species):

Ceriodaphnia dubia

Details on test organisms:

Age of test organisms: Less than 24 h; and all released within a 8-h period

Test type:

semi-static

Water media type:

other: Dilution water: moderately hard synthetic water = US EPA prescribed (US EPA, 2002) acute + chronic testing formula; balanced salt conc. + micronutr. mimic natural water providing a medium in which many organisms can survive, grow, reproduce normally

Limit test:

no

Total exposure duration:

7 d

Hardness:

see "details on test solution"

Test temperature:

25±1.5 °C

pH:

not quantified

Dissolved oxygen:

not quantified

Salinity:

freshwater test but tested mixture contains NaCl (see test substance)

Conductivity:

not quantified

Nominal and measured concentrations:

product (mixture) nominal concentrations:
0, 0.0005, 0.001, 0.002, 0.003, 0.004, 0.005, 0.100, 1 g/L
corresponding to nominal glycerin concentrations:
0, 0.2, 0.4, 0.8, 1.2, 1.6, 2.0, 40.0, 400.0 mg/L

Details on test conditions:

TEST SYSTEM
- Test chamber size 30 ml, test solution volume: 15 ml
- Aeration: no
- Renewal rate of test solution: daily
- No. of neonates per test chamber: 1. Assigned using blocking by known parentage
- No. of replicate test chanbers per concentration: 10
- No. of vessels per control (replicates): 4


OTHER TEST CONDITIONS
- Source of food: Newly hatched Artemia nauplii (less than 24 h o ld)
- Feeding regime: Feed 0.1 mL each ofYCT and algal suspension per test chamber daily
- Cleaning: Use freshly cleaned glass beakers or new plastic cups daily
- Photoperiod: 16light, 8h darkness
- Light intensity: 10-20 μE/mi/s (50-100 ft-c)(ambient laboratory levels)

- Test duration: Until 60% or more of surviving control females have three broods (maximum test duration 7 days)

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
survival, reproduction
observation at the end of exposure period reported

Key result

Duration:

7 d

Dose descriptor:

NOEC

Effect conc.:

800 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

reproduction

Remarks:

young production

Remarks on result:

other:

Validity criteria fulfilled:

not applicable

Conclusions:

For a commercial de-icer containing glycerol (content of 800mg glycerol/L derived through indirect information) chronic toxicity to the invertebrate Ceriodaphnia dubia was tested for 7 days in a semi-static (daily removal) setting. The NOEL (young production) was 1 g product /L corresponding to 800mg Glycerin /L.

Description of key information

EPS long term toxicity to aquatic invertebrates

 

 

Conclusion:

For the endpoint long-term toxicity to aquatic invertebrates, there is sufficient information for a valid conclusion on the hazard of Glycerol: 

Regarding the long-term toxicity to aquatic invertebrates, Glycerol is not hazardous up to the limit dose of 100 mg/L.

 

Description of Weight-of-evidence-approach (WoE) leading to this conclusion:

1. Glycerol as fatty acid glyceride and as metabolite of fatty acid glycerides is part of (almost) all organisms. 

For this reason, toxicity of glycerol to invertebrates does not appear likely. At least not at concentrations without relevant influence on the physicochemical properties of water. 

 

2. For a commercial de-icer containing glycerol (content of 800mg glycerol/L derived through indirect information) chronic toxicity to the invertebrate Ceriodaphnia dubia was tested for 7 days in a semi-static (daily removal) setting. The NOEL (young production) was 1 g product /L corresponding to 800mg Glycerin /L.

 

3. The chronic value for toxicity to Daphnia magna was estimated using EpiSuite™ (The Estimation Programs Interface [EPI] Suite™) software developed by the US Environmental Protection Agency´s Office of Pollution Prevention and Toxics and Syracuse Research Coroperation (SRC) in the QSAR model ECOSAR v1.11. The 16 d-ChV is 2230 mg/L

 

4. The chronic toxicity (NOEC) of Glycerol to Daphnia magna was estimated using Trend analysis of the OECD QSAR Toolbox version 4.4.1. Based on the presented trend analysis and toxicity effect levels of structurally similar substances, the NOEC for long-term exposure of Daphnia magna to glycerol was estimated to be 897 mg/L.

 

 

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

NOEC

Effect concentration:

> 100 mg/L