Copper glycinate sulfate

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across hypothesis is based on transformation of the target and source substances to common compounds (scenario 1 of the RAAF). The target substance copper monoglycinate sulfate and the source substances copper sulfate and copper bisglycinate consist of the Cu2+ cation and the respective anion. The amino acid glycine is constituent of both the target substance copper monoglycinate sulfate and the source substance copper bisglycinate.
It is generally accepted that the Cu2+ cation (as measure for dissolved copper species) is the determining factor for toxicity and ecotoxicity, but not sulfate or glycine.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance copper monoglycinate sulfate is a chelate-complex which consists of the divalent copper ion as centre-ion and glycine as ligand. The remaining sulfate group stabilizes the center ion within the complex.
Copper monoglycinate sulfate and the source substance copper sulfate are ionic and consist of the Cu2+ cation and the respective anions. It is generally accepted that the copper cation is the determining factor for toxicity and ecotoxicity. Therefore, this read-across approach is based on the assumption that the metal cation of both the target and the source substance, copper, is the relevant component for assessment of toxicity and ecotoxicity.
The anion of the target substance is the essential amino acid glycine and the sulfate anion. In the source substance, it is the sulfate anion. These anions are not considered as (eco)toxicologically relevant at the given concentrations.
Please refer to the justification for read-across analogue approach in Chapter 13.2 for more detailed information.
3. ANALOGUE APPROACH JUSTIFICATION
Please refer to the justification for read-across analogue approach in Chapter 13.2 for more detailed information.
4. DATA MATRIX
Please refer to the justification for read-across analogue approach in Chapter 13.2 for more detailed information.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Test organisms (species):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Duration:

72 h

Dose descriptor:

other: LC/EC50

Effect conc.:

0.139 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

other: Cu2+

Basis for effect:

other: growth rate or biomass

Remarks on result:

other: The given value is an average of 3 pH classes.

Key result

Duration:

72 h

Dose descriptor:

other: LC/EC50

Effect conc.:

0.59 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr.

Basis for effect:

other: growth rate or biomass

Remarks on result:

other: This LC/EC50 is a calculated value for the target substance. The given value is an average of 3 pH classes.

Validity criteria fulfilled:

not applicable

Conclusions:

The 72-h average EC50/LC50 of Copper ions towards Pseudokirchneriella subcapitata was 0.139 mg Cu/L as derived from a data collection of the respective European Union Risk Assessment Report. This refers to an EC/LC50 of copper monoglycinate sulfate dihydrate of 0.59 mg/L.

Executive summary:

The 72-h average EC50/LC50 of copper ions towards Pseudokirchneriella subcapitata was 0.139 mg Cu/L as derived from a data collection of the respective European Union Risk Assessment Report. The target substance bis(glycinato)copper is a complex of Cu²⁺ and glycine. Glycine is a naturally occurring amino acid and according to QSAR calculation, no toxic effects are expected to occur up to saturation limits.

Thus, the results from this data compilation refer to a 72-h EC50/LC50 of 0.59 mg copper monoglycinate sulfate dihydrate per Liter.

Reference 2

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

other: European Union Risk Assessment Report

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline followed

Principles of method if other than guideline:

The presented data have been collected and evaluated in an European Union Risk Assessment Report: "VOLUNTARY RISK ASSESSMENT OF COPPER, COPPER II SULPHATE PENTAHYDRATE, COPPER(I)OXIDE, COPPER(II)OXIDE, DICOPPER CHLORIDE TRIHYDROXIDE, CHAPTER 3 – ENVIRONMENTAL HAZARD CLASSIFICATION", as an UPDATE OF EU RA APPENDIX K1.

GLP compliance:

no

Remarks:

collection of data

Test organisms (species):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Test type:

other: Standard OECD approved tests and non standardised tests have been considered as suitable.

Key result

Duration:

72 h

Dose descriptor:

other: EC50 / LC50

Effect conc.:

0.139 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

other: Copper ion

Basis for effect:

other: growth rate or biomass

Remarks on result:

other: The given value is an average of 3 pH classes.

Details on results:

The results have been derived from 47 high quality acute toxicity data.

Ecotoxicity of soluble copper species

Acute ecotox values to be used for hazard classification

The data are presented in Table 1. For the algae 66 individual data points were selected for 3 standard species (Pseudokirchneriella subcapitata, Chlamydomonas reinhardtii and Chlorella vulgaris).

 Table 1: Overview of the selected high quality acute toxicity data for the individual species (L(E)C 50 values expressed as µg/l) for the 3 pH classes.

	LC/EC50 [µg/L]
Algae	pH: 5.5-6.5	pH: >6.5-7.5	pH: >7.5-8.5	all pH
Pseudokirchneriella subcapitata
n	11	18	18	47
min	92.0	30.0	36.9	30.0
max	824.0	685.0	346.0	824.0
Geometric mean/lowest value	263.5	120.1	106.8	138.9
Chlamydomonas reinhardtii
n	1	1	1	3
min	380.0	315.0	146.0	146.0
max	380.0	315.0	146.0	380.0
Geometric mean/lowest value	380.0	315.0	146.0	146.0
Chlorella vulgaris
n	5	7	4	16
min	333.0	60.0	99.0	60.0
max	987.0	446.0	506.0	987.0
Geometric mean/lowest value	582.9	232.7	214.4	296.1

 

Validity criteria fulfilled:

not applicable

Conclusions:

The 72-h average EC50/LC50 of Copper ions towards Pseudokirchneriella subcapitata was 0.139 mg Cu/L as derived from a data collection from the respective European Union Risk Assessment Report.

Executive summary:

The toxicity of soluble copper compounds was assessed in the European Union Risk Assessment Report “VOLUNTARY RISK ASSESSMENT OF COPPER, COPPER II SULPHATE PENTAHYDRATE, COPPER(I)OXIDE, COPPER(II)OXIDE, DICOPPER CHLORIDE TRIHYDROXIDE, CHAPTER 3 – ENVIRONMENTAL HAZARD CLASSIFICATION, APPENDIX K1: CLASSIFICATION: ACUTE & CHRONIC ECOTOXICITY DATA ON SOLUBLE COPPER SPECIES” and the related “UPDATE OF EU RA APPENDIX K1 “ACUTE & CHRONIC ECOTOXICITY OF SOLUBLE COPPER SPECIES IN VIEW OF HAZARD CLASSIFICATION OF COPPER AND COPPER COMPOUNDS” by Van Sprang and Delbeke.

The compilation of the acute toxicity data is based on an extensive literature search performed by J. Meyer, University of Wyoming (1999). To compile data on the effects of Cu and related compounds towards aquatic biota both extensive databases and scientific literature were consulted.

For the selection of the toxicity data, the following reliability and relevance criteria were used:

Reliability criteria

• Soluble copper compounds have been used as test compound.

• Standard OECD approved tests and non-standardised tests have been considered as suitable.

• Tests should be performed according standard operational procedures. A detailed description of methods employed in the study should be provided

• Clear dose response relationships should be observed and a NOEC/L(E)C 50 should be derived according to appropriate statistical methods.

• Since the acute & chronic effect levels are often not far above reported copper background concentrations, only effect levels based on actual (measured) concentrations have been found reliable.

• If different NOEC/L(E)C 50 values were reported, measured dissolved values were used as priority, measured total values were used as second priority.

Relevance criteria

• Only data obtained for the standard OECD test species were selected as relevant to hazard classification.

• Only standardised OECD endpoints and exposure duration were selected. Algae: EC 50 (biomass and growth rate) values (acute) and NOECs (chronic) from exposure duration of 72 hours. If both biomass and growth rates were reported, growth rate values were used for further evaluation.

• Cu-only exposures are considered relevant for the effects assessment. Studies should be rejected if indications exist that impurities or other substances might have had an effect on the toxic properties of the substance under investigation.

• Only relevant test media were considered: tests carried out in test media with pH range between 5.5 and 8.5 were selected for both the acute and chronic endpoints. No selection was based on hardness values.

• Culture conditions were not used as selection criteria but evaluated and discussed where appropriate. 

When 4 or more acceptable L(E)C 50 / NOEC values were available for the same species, the geometric mean of the toxicity values was used as representative toxicity value for that species instead of the lowest value for the species. Considering the crucial importance of pH of the test media on the copper solubility and ecotoxicity, for the acute and chronic toxicity endpoints, 3 pH categories were distinguished within the acute and chronic ecotoxicity database: pH 5.5-6.5, >6.5-7.5 and >7.5-8.5.

The geometric LC/EC50 mean across three pH-ranges in Pseudokirchneriella subcapitata, which is considered suitable for the test according to OECD guideline 201, was 0.139 mg Cu/L.

 

Reference 3

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

supporting study

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
The Estimation Programs Interface (EPI) SuiteTM v4.1 contains the ECOlogical Structure Activity Relationship (ECOSAR) software

2. MODEL (incl. version number)
ECOSAR v1.11, June 19, 2002

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS-No.: 56-40-6
SMILES: O=C(O)CN
Log Kow (measured) = at 25°C
Water solubility (measured) = 480 g/L at 20°C
Melting point (measured) = no melting point, decomposition at 325°C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
For further information, please refer to the attached QSAR reporting format

5. APPLICABILITY DOMAIN
For further information, please refer to the attached QSAR reporting format

6. ADEQUACY OF THE RESULT
For further information, please refer to the attached QSAR reporting format

Qualifier:

no guideline followed

Principles of method if other than guideline:

-Software tool(s) used including version: The Estimation Programs Interface (EPI) SuiteTM v4.1 contains the ECOlogical Structure Activity Relationship (ECOSAR) software
- 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:

96 h

Dose descriptor:

EC50

Effect conc.:

93 748.5 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: results for ECOSAR Class Aliphatic Amines

Remarks:

results from QSAR prediction

Key result

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

144 000 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: results for ECOSAR Class Neutral Organic SAR (Baseline Toxicity)

Remarks:

results from QSAR prediction

Validity criteria fulfilled:

not applicable

Remarks:

QSAR prediction

Conclusions:

In the present QSAR prediction conducted with the EPISuite TM; ECOSAR v1.11 software. The program detected two functional groups present in the molecule which are considered to exhibit a more specific mode of toxicity, namely, aliphatic amines and neutral organics moiety. In consideration of the results of the two chemical classes, two LC50 values are estimated. All LC50 values predicted for glycine are far above the 100 mg/L limit concentration. Since the substance falls within the applicability domain of the used model and the predicted values are more than 10-fold greater than the water solubility, no toxic effects are expected to occur up to saturation limits.

Executive summary:

In the present QSAR prediction conducted with the EPISuite TM; ECOSAR v1.11 software. The program detected two functional groups present in the molecule which are considered to exhibit a more specific mode of toxicity, namely, aliphatic amines and amides. In consideration of the results of all three chemical classes, several LC50 values are estimated. The LC50 value predicted for L-glycine is far above the 100 mg/L limit concentration. Since the substance falls in the applicability domain of the used model and the predicted values are more than 10-fold greater than the water solubility, no toxic effects are expected to occur up to saturation limits.

Description of key information

- Key information: Van Sprang and Delbeke, Update to Appendix K1 of the European Union Risk Assessment Report: The geometric LC/EC50 mean across three pH-ranges in Pseudokirchneriella subcapitata was 0.139 mg Cu/L as determined in standard OECD approved tests and suitable non-standardised tests. This refers to 0.59 mg copper monoglycinate sulfate dihydrate per Liter.

- Glycine, QSAR estimation: Since the substance falls within the applicability domain of the used model and the predicted values are more than 10-fold greater than the water solubility, no toxic effects are expected to occur up to saturation limits.

Key value for chemical safety assessment

EC50 for freshwater algae:

0.59 mg/L

Additional information

The toxicity of soluble copper compounds was assessed in the European Union Risk Assessment Report “VOLUNTARY RISK ASSESSMENT OF COPPER, COPPER II SULPHATE PENTAHYDRATE, COPPER(I)OXIDE, COPPER(II)OXIDE, DICOPPER CHLORIDE TRIHYDROXIDE, CHAPTER 3 – ENVIRONMENTAL HAZARD CLASSIFICATION, APPENDIX K1: CLASSIFICATION: ACUTE & CHRONIC ECOTOXICITY DATA ON SOLUBLE COPPER SPECIES” and the related “UPDATE OF EU RA APPENDIX K1 “ACUTE & CHRONIC ECOTOXICITY OF SOLUBLE COPPER SPECIES IN VIEW OF HAZARD CLASSIFICATION OF COPPER AND COPPER COMPOUNDS” by Van Sprang and Delbeke.

The compilation of the acute toxicity data is based on an extensive literature search performed by J. Meyer, University of Wyoming (1999). To compile data on the effects of Cu and related compounds towards aquatic biota both extensive databases and scientific literature were consulted.

For the selection of the toxicity data, the following reliability and relevance criteria were used:

Reliability criteria

• Soluble copper compounds have been used as test compound.

• Standard OECD approved tests and non-standardised tests have been considered as suitable.

• Tests should be performed according standard operational procedures. A detailed description of methods employed in the study should be provided

• Clear dose response relationships should be observed and a NOEC/L(E)C 50 should be derived according to appropriate statistical methods.

• Since the acute & chronic effect levels are often not far above reported copper background concentrations, only effect levels based on actual (measured) concentrations have been found reliable.

• If different NOEC/L(E)C 50 values were reported, measured dissolved values were used as priority, measured total values were used as second priority.

Relevance criteria

• Only data obtained for the standard OECD test species were selected as relevant to hazard classification.

• Only standardised OECD endpoints and exposure duration were selected. Algae: EC 50 (biomass and growth rate) values (acute) and NOECs (chronic) from exposure duration of 72 hours. If both biomass and growth rates were reported, growth rate values were used for further evaluation.

• Cu-only exposures are considered relevant for the effects assessment. Studies should be rejected if indications exist that impurities or other substances might have had an effect on the toxic properties of the substance under investigation.

• Only relevant test media were considered: tests carried out in test media with pH range between 5.5 and 8.5 were selected for both the acute and chronic endpoints. No selection was based on hardness values.

• Culture conditions were not used as selection criteria but evaluated and discussed where appropriate. 

When 4 or more acceptable L(E)C 50 / NOEC values were available for the same species, the geometric mean of the toxicity values was used as representative toxicity value for that species instead of the lowest value for the species. Considering the crucial importance of pH of the test media on the copper solubility and ecotoxicity, for the acute and chronic toxicity endpoints, 3 pH categories were distinguished within the acute and chronic ecotoxicity database: pH 5.5-6.5, >6.5-7.5 and >7.5-8.5.

The geometric LC/EC50 mean across three pH-ranges in Pseudokirchneriella subcapitata, which is considered suitable for the test according to OECD guideline 201, was 0.139 mg Cu/L.

 

In the present QSAR prediction conducted with the EPISuite TM; ECOSAR v1.11 software. The program detected two functional groups present in the molecule which are considered to exhibit a more specific mode of toxicity, namely, aliphatic amines and amides. In consideration of the results of all three chemical classes, several LC50 values are estimated. The LC50 value predicted for L-glycine is far above the 100 mg/L limit concentration. Since the substance falls in the applicability domain of the used model and the predicted values are more than 10-fold greater than the water solubility, no toxic effects are expected to occur up to saturation limits.

 

The test item is considered to be very toxic to aquatic algae and cyanobacteria according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).