Glycerol

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

long-term toxicity to fish, other

Remarks:

QSAR estimation

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

Key result

Duration:

30 d

Dose descriptor:

other: ChV; chronic value

Effect conc.:

9 471.097 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

adult mortality

Validity criteria fulfilled:

not applicable

Conclusions:

For Glycerol the QSAR estimation of chronic fish toxicity resulted in a 30d-ChV of 9471 mg/L. This result is far above the limit dose of chronic fish testing (100mg/L). According to this QSAR estimation no chronic hazard for fish can be identified.

Executive summary:

The 30-day-chronic toxicity of Glycerol to fish 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 values for toxicity to fish was calculated as follows for the neutral organics class:

ESTIMATED TOXICITY:

The fish 30-d chronic values (ChV) 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 ChV (mmol/L) = - 0.8508 log Kow + 0.6063

 

The ChV is in millimoles per liter (mM/L); N = 46 + 7; and the Coefficient of Determination (R2) = 0.7393. 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) which lies below the recommended threshold for the applicability of the model the result is considered valid. 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 30 d Fish: 9471.097 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 2

Endpoint:

long-term toxicity to fish, other

Remarks:

QSAR Toolbox Trendanalysis

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, 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 fish
- Unambiguous algorithm: linear regression from structurally similar substances
- Defined domain of applicability: structural similarity (≥50%), logKow (-0,439 to 0,58),
- 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

Key result

Dose descriptor:

NOEC

Effect conc.:

724 000 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

not specified

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:

Based on the presented trend analysis and toxicity effect levels of structurally similar substances, the NOEC for long-term exposure of fish to glycerol was estimated to be 7.24E+05 mg/L.

Executive summary:

The chronic toxicity (NOEC) of Glycerol to fish 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: undefined endpoint = 2,01 (±1,18) + 1,65 (±2,80) * Partition Coefficient: log(1/mol/L)

Active descriptor: Partition Coefficient: (experimental)

Data usage: Arithmetic mean (average) value*

Statistics of the prediction model:

N = 3; count of data points

R2 = 0,983; coefficient of determination

R2adj = 0,965; adjusted coefficient of determination

SSR = 0,0252; sum of squared residuals

s = 0,0916; sample standard deviation of residuals

F = 56,5; 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 (-0,439 to 0,58) 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 Fish: 7.24E+05 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 fish, other

Type of information:

not specified

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 4

Endpoint:

long-term toxicity to fish, other

Type of information:

experimental study

Remarks:

long term use of different doses of glycerol in fish food and observation of parameters

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The aim of the studies is to observe the effect of using different proportions of glycerol in fish feed. Observed parameters partly differ from a chronic fish study.

Principles of method if other than guideline:

This IUCLID entry doesn't refer to a test to derivate effect concentrations and thus cannot follow a guideline. Instead, this IUCLID entry describes the use of various amounts of glycerol as fish feed and observes morphometric, zootechnical and blood parameters (no adverse effects) and thus shows no hazard of Glycerol towards fish.

GLP compliance:

no

Remarks:

Information was published. For this piece of information GLP is not applicable. This report is part of a weight-of-evidence approach and all pieces together result in the conclusion. No GLP therefore is sufficient.

Remarks on result:

other: use of glycerol as part of fish feed, no effect concentration determined

Zootechnical performance parameters of silver catfish (R. quelen) fingerlings fed diets containing increasing levels crude glycerol in substitution for corn.  

variables	0	20	40	60	80	100	p-values
Headless carcass yield (%) ^2 Clean trunk yield (%) ^2 Specific growth rate (% / day) ^1 Hepatosomatic index (%) ^2 Apparent feed conversion ^1 Feed efficiency ^1 Condition fator ^1 Protein efficiency rate ^1	52.57 ± 1.72  24.36 ± 5.12  4.17 ± 0.05  1.91 ± 0.07  1.65 ± 0.17  67.92 ± 7.02  0.97 ± 0.02  1.87 ± 0.19	53.58 ± 0.64  24.29 ± 2.31  4.19 ± 0.13  2.07 ± 0.48  1.40 ± 0.15  81.65 ± 2.80  0.98 ± 0.03  2.26 ± 0.08	52.45 ± 1.15  29.21 ± 0.84  4.11 ± 0.26  2.05 ± 0.41  1.64 ± 0.29  73.97 ± 3.74  1.00 ± 0.01  2.06 ± 0.10	51.41 ± 2.94  27.91 ± 2.39  4.18 ± 0.09  1.97 ± 0.08  1.53 ± 0.19  74.27 ± 9.38  0.98 ± 0.04  2.06 ± 0.26	53.07 ± 0.87  25.77 ± 5.16  4.33 ± 0.11  2.04 ± 0.27  1.37 ± 0.35  84.36 ± 19.94  1.01 ± 0.04  2.35 ± 0.56	52.87 ± 2.90  26.11 ± 1.65  4.07 ± 0.07  2.22 ± 0.19  1.67 ± 0.15  70.17 ± 7.77  1.01 ± 0.05  1.96 ± 0.22	0.75  0.38  0.22  0.78  0.29  0.24  0.11  0.23

¹ Parameters analyzed using all fish surviving the treatments.
² Three fish per experimental unit, totaling 12 per treatment. 

 

Blood parameters of silver catfish (R. quelen) fingerlings fed diets containing increasing levels crude glycerol in substitution for corn.

Variables ^1	Diets (% corn replacernent for glycerol)						p-
							value
	0	20	40	60	80	100
Calcium (mg dl-^1)	14.27 ± 0.15	13.25 ± 1.77	12.08 ± 1.61	14.28 ± 0.98	14.18 ± 0.25	12.94 ± 1.51	0.17
Cholesterol (mg dl-^1)	155.54 ± 8.33	174.50 ± 15.78	165.50 ± 42.02	159.22 ± 4.53	167.92 ± 26.18	149.17 ± 23.23	0.73
Alkaline phosphatase (mg dl-^1)	77.08 ± 4.57	81.79 ± 7.80	82.00 ± 17.90	66.06 ± 3.81	79.00 ± 1.45	77.42 ± 5.74	0.30
Glucose (mg dl-^1)*	170.98 ± 18.99ab	205. 93 ± 35.05a	202.70 ± 55.40ab	135.37 ± 21.18b	171.68 ± 23.37ab	184.58 ± 11.76ab	0.04
Totalproteins (g dl-^1)	3.83 ± 0.24	4.06 ± 0.27	3.76 ± 0.15	3.72 ± 0.13	3.79 ± 0.41	3.99 ± 0.13	0.30
Glutamic oxalacetic transaminase (UI^-1)	91.40 ± 16.99	154.11 ± 77.27	114.76 ± 6.93	108.23 ± 38.48	89.28 ± 13.68	166.62 ± 99.49	0.30
Pyruvic glutamic transaminase (UI^-1)	12.63 ± 1.70	16.11 ± 7.00	17.95 ± 5.51	12.83 ± 4.81	11.88 ± 3.47	18.49 ± 10.03	0.51
Triglycerides (mg dl^-1)	495.92 ± 141.01	580.58 ± 34.96	584.00 ± 163.64	588. 92 ± 94.50	550.83 ± 69.26	527.67 ± 151.44	0,85

 

1 Blood samples from three fish per experimental unit were analyzed, totaling 12 animals per treatment.

* Means followed by the same letter on the line, do not differ statistically at 5% probability by the Tukey test.

 

 

Conclusions:

It is concluded that silver catfish fingerlings display the ability to use crude glycerol as an energy ingredient in their diets in up to 7.5% of inclusion, or even totally replacing corn in food, without affecting morphometric, performance parameters or causing health damage. No adverse effects are observed.

Executive summary:

Up to 7.5% glycerine in regular food (six treatment goups of fish, 200 fish per treatment (1200 in total), from 0% to 7.5% glycerine in food) for silver catfish fingerlings (Ramdia quelen) is tested for 75 days.
It is concluded that silver catfish fingerlings display the ability to use crude glycerol as an energy ingredient in their diets in up to 7.5% of inclusion, or even totally replacing corn in food, without affecting morphometric, performance parameters or causing health damage.

Reference 5

Endpoint:

long-term toxicity to fish, other

Type of information:

not specified

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: publication of glycerol in fish feed for aquaculture

Principles of method if other than guideline:

This IUCLID entry doesn't refer to a test and thus cannot follow a guideline. Instead, this IUCLID entry shows the use of glycerol as fish feed and thus shows no hazard of Glycerol towards fish.

GLP compliance:

no

Remarks:

Information was published. For this piece of information GLP is not applicable. This report is part of a weight-of-evidence approach and all pieces together result in the conclusion. No GLP therefore is sufficient.

Remarks on result:

other: use of glycerol as part of fish feed, no effect concentration determined

Conclusions:

Glycerol is used as part of commercial fish feed. And thus shows no hazard towards fish.

Executive summary:

Glycerol is used as part of commercial fish feed and can replace a part of maize in feed. This is reported in this literature for the following fish species used in aquaculture:
Cyprinus carpio,Ictalurus punctatus, Oreochromis niloticus, Piaractus mesopotamicus, Prochilodus lineatus, Rhamdia quelen, Rhamdia voulezi, Rhamdia branneri, Salmo gairdneri

Description of key information

Conclusion:

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

Regarding the long-term toxicity to fish, Glycerol is not hazardous to fish 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 fish does not appear likely. At least not at concentrations without relevant influence on the physicochemical properties of water. 

 

2. Glycerol is used as part of commercial fish feed. And as such shows no hazard towards fish in tested fish feed concentrations up to 7.5% for 12 month.

3. Following one exemplary study on the use of Glycerol as fish feed and examination of metabolic parameters: It is concluded that silver catfish fingerlings display the ability to use crude glycerol as an energy ingredient in their diets in up to 7.5% of inclusion, or even totally replacing corn in food, without affecting morphometric, performance parameters or causing health damage. No adverse effects are observed.

For the uptake of Glycerol with feed (concentration in feed up to 7.5%) for 12 month, no adverse effects are observed. 

 

4.+5.

In addition, two QSAR models were used to estimate the NOEC of Glycerol for the endpoint long-term toxicity to fish:

ECOSAR (v1.11 as part of EpiSuite)

QSAR Toolbox (4.4.1), trend analysis

The outcome of both QSAR models shows the long-term NOEC above the limit dose of 100mg/L.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

NOEC

Effect concentration:

> 100 mg/L