Bis(D-gluconato-O1,O2)zinc

Toxicity to microorganisms

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

activated sludge respiration inhibition testing

Type of information:

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

Adequacy of study:

key study

Study period:

1983

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

Key result

Duration:

3 h

Dose descriptor:

EC50

Effect conc.:

5.2 mg/L

Nominal / measured:

not specified

Conc. based on:

not specified

Basis for effect:

inhibition of total respiration

Duration:

0.5 h

Dose descriptor:

EC50

Effect conc.:

6.1 mg/L

Nominal / measured:

not specified

Conc. based on:

not specified

Basis for effect:

inhibition of total respiration

Validity criteria fulfilled:

yes

Conclusions:

Tests done under conditions similar to standard protocol. This study is considered reliable. In the EU risk assessment report on Zinc (2010) this value is considered as the lowest useful EC50 value (for bacteria) for setting the PNEC for STP.

Executive summary:

Study compares the effect of different substances , e.g. zinc on different microbiological parameters. This study is considered reliable. The EC50 for sludge respiration inhibition was used in the risk assessment for setting the PNEC for STP.

Reference 2

Endpoint:

toxicity to microorganisms, other

Type of information:

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

Adequacy of study:

supporting study

Study period:

2002

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:

3 h

Dose descriptor:

IC50

Effect conc.:

> 10 mg/L

Nominal / measured:

nominal

Conc. based on:

not specified

Basis for effect:

inhibition of total respiration

Duration:

3 h

Dose descriptor:

IC50

Effect conc.:

10 mg/L

Nominal / measured:

nominal

Conc. based on:

not specified

Basis for effect:

inhibition of nitrification rate

Details on results:

The following other parameters were also measured but considered of less relevancy for the REACH registration dossier: Vibrio fischeri toxicity test, ATP bioluminescence test (very insenssitive to zinc), enzyme inhibition .

Reported statistics and error estimates:

Error bars are graphically reported, are very small (number of tests respiration: 11; for nitrification inhibition: 10)

Validity criteria fulfilled:

yes

Conclusions:

Tests done according to standard protocol. Good quality and considered relevant for assessment.

Executive summary:

Five rapid direct toxicity assessment methods were used in 3 EU member states. Nitrification inhibition and respiration were measured. The IC50 for respiration was graphically derived as > 10mg Zn/l, the IC50 for nitrification inhibition was 10mg Zn/l.

Description of key information

As reported in the Eu risk assessment report (EU RAR 2010), the activated sludge respiration inhibition test reported by Dutka et al. (1983) showed the lowest useful EC50 value (for bacteria) for Zinc compounds, with a 3-h EC50 of 5,200 μg/l. This value is considered for assessment in a read-across approach.

Key value for chemical safety assessment

EC50 for microorganisms:

5.2 mg/L