Reaction products of sodium glucoheptonate with zinc sulfate and sodium hydroxide

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
An extended read-across statement is attached under section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Skin sensitisation potential of glucoheptonates is believed to be driven by metal cation bonded to the organic part of the molecule and not by the organic part itself. Glucohepotonates can dissociate on the skin releasing their metals that can further interact with skin proteins, while no skin sensitisation potential can be attributed to the organic part of the molecule. Glucoheptonates are not known to bind to proteins, producing a hapten eliciting a skin sensitisation response.
Therefore, data on skin sensitisation potential of several organic and inorganic compounds have been taken into account to address skin sensitisation potential of zinc cation which could be released from the zinc glucoheptonate in contact with skin.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Information on purity of the registered substance is provided in the target record under "Test material" as confidential. The content of zinc glucoheptonate in the registered product is 75 %. Another component is Na2SO4. Sodium is a macroelement occuring in surface waters and in living organisms in considerable amounts. Sulfur species are also found in living organisms. Thus, these cations and anions are considered not to impact the sensitisation of zinc to mammals.
There is limited information on purity of the source substance zinc gluconate.

3. ANALOGUE APPROACH JUSTIFICATION
Zinc gluconate (source) and Sodium Zinc glucoheptonate complex (HGA:Zn-1:1) (target) are structurally very similar. Both - the source and the target substance - contain the same types of hydrocarbon constituents (sugar residues), which are only variable in carbon chain length. In case of zinc gluconate two gluconic acid-chains (C6H11O7-) are involved and in case of zinc glucoheptonate it is two glucoheptonic acid chains (C7H10O8).
It has generally been shown by a substantial body of evidence, that the toxicity profiles of chelate compounds in general depend mainly on metal ion, its affinity to this metal, and their ability to supply or to sequester it from the body. In the OECD SIDS report is mentioned “Evidence from the reviewed literature suggests that the eventual toxicity of the gluconate salts would be attributable to the cation rather than to the gluconate moiety of these substances.”

4. DATA MATRIX
please refer to the detailed data matrix attached in section 13.

Materials and methods

Study type:

other: review article

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of sodium glucoheptonate with zinc sulfate and sodium hydroxide

EC Number:

946-329-1

Molecular formula:

Not specified (UVCB substance).Molecular formula of the main substance:C14H30O22SZn2

IUPAC Name:

Reaction products of sodium glucoheptonate with zinc sulfate and sodium hydroxide

Test material form:

solid: granular

Remarks:

microgranulated

Results and discussion

Any other information on results incl. tables

Zinc gluconate, also called zincum gluconicum, is the zinc salt of gluconic acid. It has been shown to be efficient to treat inflammatory skin diseases such as acne vulgaris. Recent studies revealed that its antiinflammatory

effects may target at peroxisome proliferator-activated receptors-α (PPARs-α), human β-defensin-2, and psoriasin.

Applicant's summary and conclusion

Executive summary:

Zinc gluconate, also called zincum gluconicum, is the zinc salt of gluconic acid. It has been shown to be efficient to treat inflammatory skin diseases such as acne vulgaris. Recent studies revealed that its antiinflammatory effects may target at peroxisome proliferator-activated receptors-α (PPARs-α), human β-defensin-2, and psoriasin. This anti-inflammatory activity of Zinc gluconate may prevent the initiation of skin sensitisation. This is of high relevance for the target substance zinc glucoheptonate, because it is very similar to zinc gluconate. Therefore, an identical effect can be expected for zinc glucoheptonate.