Bis(D-gluconato-O1,O2)zinc

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:

weight of evidence

Study period:

2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The read-across hypothesis is instantaneous dissociation of zinc gluconate into zinc cations (Zn2+) and gluconate anions in aqueous media (environmental compartments and body fluids). Thus, for endpoints where no zinc gluconate data exist, the assessment of the (eco-) toxicological effects can be based on available data of dissociable zinc compounds and gluconate derivatives.
The assessment of human and environmental toxicology is mainly based on the zinc ion, which is considered to be toxicologically more relevant than the gluconate ion (see complete justification report attached).
All of the zinc based read-across partners have in common that they dissociate into zinc and the respective counter ion in aqueous media as described above. The same is true for all of the gluconate based read-across partners, as they dissociate into the gluconate anion and the respective counter ion in aqueous media.
The gluconate derivatives are tentatively ignored for the purpose of this read-across due to the role of gluconates as common additives or nutritional supplements in food and due to the fact that gluconate/gluconic acid is a ubiquitous metabolic product/substrate in mammals with proven low toxicity. As a normal metabolic product of glucose metabolism, 25–30 g are being produced daily in humans. It can safely be concluded that systemic toxicity need not be expected to arise from gluconates/gluconic acid when assessing the potential effects of zinc gluconate. Nevertheless, the lack of toxicological relevance of gluconates is addressed in sufficient detail in the final read-across report targeted at supporting this dossier.
When resorting to dissociable zinc read-across partners, there is a risk of confounding effects that might actually be attributable to the counter ion. The dissociation products of the aforementioned zinc compounds are glycerol, sulphate and chloride ions. The counter ions of the gluconates are sodium, calcium and manganese. All these ions play an important role in the physiology of man and other species. Considering this information, the respective counter ions (calcium, sodium, manganese) are unlikely to contribute to any confounding effects hence do need to be further addressed in this report.

Taking into account the global approach and the detailed explanation (including data matrix and analysis for each endpoint) provided in the report attached, the present read-across is considered relevant.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: 72 h growth inhibition of algae, test designed for dose-response
- Short description of test conditions: The species used are not the ones recommended in the OECD guidline.

GLP compliance:

not specified

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

110 µg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

element (dissolved fraction)

Basis for effect:

growth rate

Duration:

72 h

Dose descriptor:

EC10

Effect conc.:

28 µg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

element (dissolved fraction)

Basis for effect:

growth rate

Reported statistics and error estimates:

The IC50, IC25 and IC10 were calculated using Linear Interpolation in ToxCalc Version 5.0.23 (Tidepool Software). The Students t-test (p ≤ 0.05) was used to determine significant difference between treatments.

Validity criteria fulfilled:

yes

Conclusions:

The mean 72-h IC50 was 110 ± 41μg Zn L-1.

Executive summary:

A 72h algae growth inhibition test was used to examine the toxicity of zinc to Chlorella sp. The mean EC10 value for inhibition of cell division from 4 tests is 28 ± 21 µg/L.

The mean EC50 value for inhibition of cell division from 4 tests is 110 ± 41 µg/L.

Reference 2

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The read-across hypothesis is instantaneous dissociation of zinc gluconate into zinc cations (Zn2+) and gluconate anions in aqueous media (environmental compartments and body fluids). Thus, for endpoints where no zinc gluconate data exist, the assessment of the (eco-) toxicological effects can be based on available data of dissociable zinc compounds and gluconate derivatives.
The assessment of human and environmental toxicology is mainly based on the zinc ion, which is considered to be toxicologically more relevant than the gluconate ion (see complete justification report attached).
All of the zinc based read-across partners have in common that they dissociate into zinc and the respective counter ion in aqueous media as described above. The same is true for all of the gluconate based read-across partners, as they dissociate into the gluconate anion and the respective counter ion in aqueous media.
The gluconate derivatives are tentatively ignored for the purpose of this read-across due to the role of gluconates as common additives or nutritional supplements in food and due to the fact that gluconate/gluconic acid is a ubiquitous metabolic product/substrate in mammals with proven low toxicity. As a normal metabolic product of glucose metabolism, 25–30 g are being produced daily in humans. It can safely be concluded that systemic toxicity need not be expected to arise from gluconates/gluconic acid when assessing the potential effects of zinc gluconate. Nevertheless, the lack of toxicological relevance of gluconates is addressed in sufficient detail in the final read-across report targeted at supporting this dossier.
When resorting to dissociable zinc read-across partners, there is a risk of confounding effects that might actually be attributable to the counter ion. The dissociation products of the aforementioned zinc compounds are glycerol, sulphate and chloride ions. The counter ions of the gluconates are sodium, calcium and manganese. All these ions play an important role in the physiology of man and other species. Considering this information, the respective counter ions (calcium, sodium, manganese) are unlikely to contribute to any confounding effects hence do need to be further addressed in this report.

Taking into account the global approach and the detailed explanation (including data matrix and analysis for each endpoint) provided in the report attached, the present read-across is considered relevant.

Reason / purpose for cross-reference:

read-across source

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

226 µg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

element (dissolved fraction)

Basis for effect:

growth rate

Duration:

72 h

Dose descriptor:

EC10

Effect conc.:

84 µg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

element (dissolved fraction)

Basis for effect:

growth rate

Reported statistics and error estimates:

The IC50, IC25 and IC10 were calculated using Linear Interpolation in ToxCalc Version 5.0.23 (Tidepool Software). The Students t-test (p ≤ 0.05) was used to determine significant difference between treatments.

Validity criteria fulfilled:

yes

Conclusions:

The mean 72-h IC50 was 273 ± 58μg Zn L-1.

Executive summary:

A 72h algae growth inhibition test was used to examine the toxicity of zinc to the marine diatom N. closterium. The mean EC10 value for inhibition of cell division from 4 tests is 84 ± 64 µg/L.

The mean EC50 value for inhibition of cell division from 4 tests is 226 ± 105 µg/L.

Reference 3

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
The read-across hypothesis is instantaneous dissociation of zinc gluconate into zinc cations (Zn2+) and gluconate anions in aqueous media (environmental compartments and body fluids). Thus, for endpoints where no zinc gluconate data exist, the assessment of the (eco-) toxicological effects can be based on available data of dissociable zinc compounds and gluconate derivatives.
The assessment of human and environmental toxicology is mainly based on the zinc ion, which is considered to be toxicologically more relevant than the gluconate ion (see complete justification report attached).
All of the zinc based read-across partners have in common that they dissociate into zinc and the respective counter ion in aqueous media as described above. The same is true for all of the gluconate based read-across partners, as they dissociate into the gluconate anion and the respective counter ion in aqueous media.
The gluconate derivatives are tentatively ignored for the purpose of this read-across due to the role of gluconates as common additives or nutritional supplements in food and due to the fact that gluconate/gluconic acid is a ubiquitous metabolic product/substrate in mammals with proven low toxicity. As a normal metabolic product of glucose metabolism, 25–30 g are being produced daily in humans. It can safely be concluded that systemic toxicity need not be expected to arise from gluconates/gluconic acid when assessing the potential effects of zinc gluconate. Nevertheless, the lack of toxicological relevance of gluconates is addressed in sufficient detail in the final read-across report targeted at supporting this dossier.
When resorting to dissociable zinc read-across partners, there is a risk of confounding effects that might actually be attributable to the counter ion. The dissociation products of the aforementioned zinc compounds are glycerol, sulphate and chloride ions. The counter ions of the gluconates are sodium, calcium and manganese. All these ions play an important role in the physiology of man and other species. Considering this information, the respective counter ions (calcium, sodium, manganese) are unlikely to contribute to any confounding effects hence do need to be further addressed in this report.

Taking into account the global approach and the detailed explanation (including data matrix and analysis for each endpoint) provided in the report attached, the present read-across is considered relevant.

Reason / purpose for cross-reference:

read-across source

Duration:

48 h

Dose descriptor:

EC10

Effect conc.:

350 µg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

element (dissolved fraction)

Basis for effect:

growth rate

Remarks on result:

other: test at pH 6.0

Duration:

48 h

Dose descriptor:

EC10

Effect conc.:

105 µg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

element (dissolved fraction)

Basis for effect:

growth rate

Remarks on result:

other: test at pH 6.5

Duration:

48 h

Dose descriptor:

EC10

Effect conc.:

93 µg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

element (dissolved fraction)

Basis for effect:

growth rate

Remarks on result:

other: test at pH 7.0

Duration:

48 h

Dose descriptor:

EC10

Effect conc.:

16 µg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

element (dissolved fraction)

Basis for effect:

growth rate

Remarks on result:

other: test at pH 7.5

Duration:

48 h

Dose descriptor:

EC10

Effect conc.:

5.9 µg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

element (dissolved fraction)

Basis for effect:

growth rate

Remarks on result:

other: test at pH 8.0

Details on results:

The "MDEC" = minimum detectable effect concentration is reported. This is similar to the EC10 as follows also from the comparison with dose-response curves given in figure 1. No NOECs reported.

Validity criteria fulfilled:

yes

Conclusions:

Good quality study considered acceptable for assessment.

Executive summary:

Thi study investigate the effect of different pH on the toxicity of zinc to Chlorella sp. Tests are not done according to guideline, but of good quality (acceptable scientific principles and well documented) and considered useful for assessment.

Reference 4

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 201 (Freshwater Alga and Cyanobacteria, Growth Inhibition Test)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Name of test item (zinc gluconate) : LCE11031 (BPL11-0010.001) ; Batch N° 1106900005

Analytical monitoring:

yes

Details on sampling:

At the beginning and at the end of test, aliquot (approximately 20 mL) was taken in each group containing the test item and in the control. These aliquots were transferred to ICP unit to be analyzed for zinc contents determination.

Vehicle:

no

Test organisms (species):

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

Details on test organisms:

TEST ORGANISM
- Common name: microalga
- Strain: Pseudokirchneriella subcapitata
- Source (laboratory, culture collection): from the SGS culture lab.
- Method of cultivation: Temperature at 23°C +/-2°C ; continuous light between 6000 an 10000 Lux ; in freshwater

ACCLIMATION
Number of algal cells is measured by optical density with a spectrophotometer. A calibration curve is regularly controlled by determination of cell number with Malassez cell and microscopic observation.

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

72 h

Remarks on exposure duration:

Standard exposure duration.

Test temperature:

23°C ± 2°C

pH:

8.1 ± 0.2

Nominal and measured concentrations:

5 concentrations were prepared at approximatively 0.1 - 0.2 - 0.4 - 0.8 - 1.6 mg/L

Details on test conditions:

TEST SYSTEM
- Initial cells density: 10000 cells per mL
- No. of vessels per concentration (replicates): 4 replicates : 3 replicates was inoculated whereas 1 was used as colour blanck.
- No. of control replicates: 6 replicates (with test media only)

GROWTH MEDIUM
- Standard medium used: yes

OTHER TEST CONDITIONS
- Photoperiod: continuous
- Light intensity and quality: between 6900 & 7050 Lux.

TEST CONCENTRATIONS
- Test concentrations: 0.01 - 0.1 - 1 - 10 - 100 mg/L

Reference substance (positive control):

no

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

0.26 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

growth rate

Details on results:

The EC50-72h on Pseudokirchneriella subcapitata is determined at 0.26mg/L (Confidence limits (95%) 0.23- 0.30mg/L).

Reported statistics and error estimates:

Confidence limits (95%) 0.23- 0.30mg/L

Validity criteria fulfilled:

yes

Conclusions:

The EC50-72h on Pseudokirchneriella subcapitata is determined at 0.26mg/L (Confidence limits (95%) 0.23- 0.30mg/L).

Executive summary:

An OECD 201 test was peformed on zinc gluconate. The study is considered as reliable (guideline study with GLP certificate). The EC50-72h on Pseudokirchneriella subcapitata is determined at 0.26mg/L (Confidence limits (95%) 0.23- 0.30mg/L).

Description of key information

An EC50 -72h on pseudokirchneriella subcapitata is determined at 0.26mg/L. This resulte is reliable an used for assessment.

Several EC50 and EC10 are provided as a weight of evidence, by different studies identified in a read-across approach. All these values established in these studies are in the same order of magnitude. They support the result of the experimental study.

Key value for chemical safety assessment

EC50 for freshwater algae:

0.26 mg/L