Bis(D-gluconato-O1,O2)zinc

Endpoint summary

Description of key information

Two main studies on skin sensitisation are identified in a read-across approach. The LLNA study (ikarashi et al.) is the main study used for assessing the potential for skin sensitisation.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

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

Adequacy of study:

supporting study

Study period:

1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

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

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

50%

Adequacy of challenge:

not specified

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

5

Total no. in group:

10

Clinical observations:

skin reactions of grade 1

Remarks on result:

no indication of skin sensitisation

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

skin reactions of grade 1

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

2

Total no. in group:

5

Clinical observations:

skin reactions of grade 1

Remarks on result:

no indication of skin sensitisation

Reading:

rechallenge

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

2

Total no. in group:

5

Clinical observations:

skin reactions of grade 1

Remarks on result:

no indication of skin sensitisation

As the skin reactions were comparable among the experimental and control animals, and as there was poor consistency of the skin reactions among individual experimental animals after the first and second challenge, the observed skin reactions can be considered to be non-specific signs of irritation.

Interpretation of results:

GHS criteria not met

Conclusions:

Zinc sulphate do not induce hypersensitivity in experimental animals. This conclusion can be used in a read-across approach (on analogue).

Executive summary:

The skin sensitising potential of zinc sulphate (ZnSO4.7H2O) was investigated in guinea pigs. A well-performed maximisation test, conducted according to Directive 96/54/EC B.6 and OECD guideline 406, was carried out in female Dunkin Hartley guinea pigs.

Based on the results of a preliminary study, in the main study 10 experimental animals were intradermally injected with a 0.1% concentration and epidermally exposed to a 50% concentration. Five control animals were similarly treated, but with vehicle (water) alone. Approximately 24 h before the epidermal induction exposure all animals were treated with 10% SDS. Two weeks after the epidermal application all animals were challenged with a 50% test substance concentration and the vehicle. A second challenge followed one week after the first.

In response to the 50% test substance concentration, in some experimental animals and controls skin reactions of grade 1 were observed 48 hours after the first (5/10 and 2/5, respectively) and the second challenge (4/10 and 2/5, respectively).

As the skin reactions were comparable among the experimental and control animals, and as there was poor consistency of the skin reactions among individual experimental animals after the first and second challenge, the observed skin reactions can be considered to be non-specific signs of irritation.

Hence, it can be concluded that zinc sulphate did not induce hypersensitivity in experimental animals.

Reference 2

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

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

Adequacy of study:

key study

Study period:

1992

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

Positive control results:

Not reported

Parameter:

SI

Value:

1.41

Test group / Remarks:

10 % zinc sulfate

Disintegrations per minute (DPM): Mean value cpm ± SD ( x 10-3) = 2.14 ± 0.77

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the test, the test material was determined to be non-sensitising to mice.

Executive summary:

A study was conducted to evaluate the skin sensitisation potential of the test material in mouse using a modified Local Lymph Node Assay. No guideline or GLP compliance was documented in the study report.

Groups of BALB/c mice (n=3) were treated with 10% concentration of test material or vehicle (20% ethanol solution) by applying 25 µL to the dorsum of both abraded ears for three consecutive days. Four days following the initial application, draining lymph nodes were excised. A single cell suspension of LNC was prepared and the incorporation of [3H]TdR was measured using a liquid scintillation counter.

[3H]TdR incorporation (expressed as mean counts per min (cpm) ± standard deviation per node x 10-3) was 2.14 ± 0.77 and the ratio of the proliferation in treated group to that in vehicle control (stimulation index) was 1.41.

Hence, under the conditions of the test, the test material was determined to be non-sensitising to mice.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Justification for classification or non-classification

No potential for skin sensitisation is identified in the existing studies. Thus, no classification is needed according to GHS criteria.