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Link to relevant study record(s)

Reference
Endpoint:
dermal absorption, other
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
25.02.2019
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
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSAR R6
Specific details on test material used for the study:
SMILES:O=S(=O)(O{-}.[Na]{+})O{-}.[Na]{+}_O=S1(=O)O{-}.[Cu]{2+}.O{-}1_OCC{P-}(O)C{P-}(O)C{P+}(O)C{P-}(O)C(=O)O{-}.[Cu]{2+}.O{-}C(=O)C{P-}(O)C{P+}(O)C{P-}(O)C{P-}(O)CO
Conclusions:
The value obtained of the prediction was 5.14.

Description of key information

The value obtained of the prediction was 5.14 for toxicokinetics metabolism and distribution in dermal absorption.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
5.14
Absorption rate - inhalation (%):
100

Additional information

The following information is taken into account for any hazard / risk assessment:

Experimental toxicokinetic studies are not available. The log P of – 3.11 is not suggestive of accumulation of unchanged copper di-D-gluconate/copper (2+) bis(2,3,4,5,6-pentahydroxyhexanoate) in fatty tissues subsequent to absorption from gastro-intestinal tract or from lungs. However, on the basis of the molecular structure primarily elimination is expected through bile, with small amounts eliminated in urine, sweat, and epidermal shedding.

Elimination is assumed to be rapid according to the information provided on in silico studies:   BAF (mid-trophic): -0.0277 log(L/kg wet)

Therefore, no potential for bioaccumulation is to be expected.

Additional information:

Assessment of oral toxicokinetics based on the physicochemical properties of copper di-D-gluconate / copper (2+) bis(2,3,4,5,6-pentahydroxyhexanoate):

- Molecular weight= 453.84 g/mol

- Water solubility= >1000 g/L

- Partition coefficient log P = -3.11

The following remarks on the toxicokinetics of copper di-D-gluconate / copper (2+) bis(2,3,4,5,6-pentahydroxyhexanoate) are based on the available studies. Experimental toxicokinetic studies were not available.

ABSORPTION

The physicochemical characteristics of copper di-D-gluconate / copper (2+) bis(2,3,4,5,6-pentahydroxyhexanoate) (log Pow -3.11) and the molecular mass suggest a low absorption from the gastro-intestinal tract subsequent to oral ingestion. Since only in silico data was generated for chronic toxicity, it was not possible to extrapolate an oral absorption value.

Therefore, a default oral absorption value of 100% was used.

N-octanol/water partition coefficient and molecular weight of copper di-D-gluconate / copper (2+) bis(2,3,4,5,6-pentahydroxyhexanoate) are not in ranges that favour dermal absorption.

It was confirmed by in silico studies.

DISTRIBUTION and METABOLISM

The structure of copper di-D-gluconate / copper (2+) bis(2,3,4,5,6-pentahydroxyhexanoate) suggests that after oral ingestion, it will be distributed and metabolised according to homeostasis. Liver is the major organ involved in copper homeostasis.

Once absorbed, the metal passes through basolateral membrane and transported to the liver bounded to the serum albumin, ceruloplasmin, or low-molecular mass complexes. In blood, copper is distributed into a nonexchangeable red cell pool, a plasma pool associated with proteins, and a labile pool of low molecular mass complexes. In humans, approximately 80-90% of the plasma copper is tightly bound with ceruloplasmin while the rest is bound to albumin and amino acids. intestinal copper uptake primarily occurs in the small intestine.

It will preferably be metabolized by biotransformation bounding to the carrier protein, metallothionein.

ELIMINATION

The n-Octanol/water partition coefficient (log Pow of -3.11) is suggestive of a high lipophobicity of copper di-D-gluconate / copper (2+) bis(2,3,4,5,6-pentahydroxyhexanoate) subsequent to absorption from gastrointestinal tract or from lungs. Rapid elimination is expected considering its BAF (mid-trophic) values (-0.0277 L/kg).

On the basis of the molecular structure excretion into bile is assumed to be a preferred route of elimination with small amounts eliminated though urine, sweat and epidermal shedding.

Therefore, no potential for bioaccumulation is to be expected.