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Description of key information

Key information:

  •  In an in-vitro skin irritation study according to OECD 439 (Human Skin Model Test), sodium selenate and sodium selenite were found to be irritating to the human skin.
  • In an in vitro skin irritation study according to OECD 439 (), zinc selenite was found to be non-irritating to the human skin.
  • In an in-vitro skin irritation study according to OECD 431 (Human Skin Model Test), sodium selenate and sodium selenite were found to be non-corrosive to the human skin.
  • In an in-vitro bovine corneal opacity and permeability test for identifying ocular corrosives and severe irritants according to OECD 437, sodium selenate was found to be non-corrosive and/or no eye irritant.
  • In an in-vitro bovine corneal opacity and permeability test for identifying ocular corrosives and severe irritants according to OECD 437, sodium selenite was found to be an eye irritant
  • In an in vivo OECD 405 test with rabbits, zinc selenite was found to be non-corrosive and/or no eye irritant

All studies are GLP-compliant and of high quality (Klimisch 1).

Key value for chemical safety assessment

Additional information

Background

 

A read-across category-approach is used for the assessment of the toxicological properties of selenium and selenium compounds. The following Se-substance are included in the category:

  • Se-metal (massive, powder)
  • Disodium selenate
  • Disodium selenite
  • Selenium dioxide / selenious acid
  • Zinc selenite
  • Barium selenite

A detailed rationale for the read-across hypothesis has been outlined in the read-across report that was generated according to the principles laid out in the Read-Across Assessment Framework (RAAF). In summary, the physico-chemical behavior of elemental selenium (once it has formed an ion-from its metal state), disodium selenite, disodium selenate and selenium dioxide/selenious acid is the same with regard to their metabolic fate. All selenium compounds (organic and inorganic, including elemental selenium), do share the very same metabolic fate in that after their resorption, reduction to the selenide moiety [Se2-], which is the single common precursor for its further metabolic conversion, takes place.

Therefore, there seems to be good evidence that different selenium moieties will behave very similar also for their ability to form reactive species which may play a decisive role in the generation of cytotoxicity followed likewise by unspecific and secondary clastogenicity and read-across can be made from the available data for disodium selenite. It is concluded that additional testing for each individual member of the proposed Se-category is not necessary and scientifically not meaningful.

In the case of inorganic salts like barium selenite and zinc selenite, uptake is always associated with a dissolution of the substance, i.e. dissociation into the metal cation (Zn2+, Ba2+) and the selenite anion (SeO32-). It can safely be assumed that the selenium/selenite moiety of barium/zinc selenite is generally of higher toxicological relevance than the zinc/barium cations. Therefore, the subsequent assessment of the toxicity of barium/zinc selenite focuses on the selenium moiety. As no in vivo toxicokinetic data or in vitro bioaccessibility data are available for a comparative assessment of relative bioavailability of various selenite substances, water solubility is adopted as a surrogate for bioavailability. Disodium selenite is readily soluble, with a water solubility of 800-900 g/L at 20°C. Barium selenite and zinc selenite, on the other hand, are poorly soluble salts (water solubility at 20°C of 66.7 mg/L and 16 mg/L, respectively, i.e. a difference of four/five orders of magnitude). Based on that, an intrinsically very conservative read-across from highly soluble forms to the poorly soluble barium/zinc selenite is proposed as the latter are assumed to have a lower solubility. It should also be noted that selenite anions in the tests with disodium selenite are formed under most physiological relevant conditions (i.e. neutral pH), thus facilitating unrestricted read-across between the various substances. In slightly acid conditions (pKa:8.32) the hydrogen selenite ion (HSeO3-) is formed whereas in more acidic conditions (pKa:2.62) the formation of selenious acid is observed (H2SeO3). Based on such existing equilibrium conditions, read-across between selenites, hydrogen selenites and selenious acid (solubility of 1670 g/L at 20°C) is justified.

 

Read-across from sodium selenite and selenious acid to barium/zinc selenite

Based on a comparison between toxicity reference values of zinc compounds and selenium compounds, it can safely be assumed that the selenium/selenite moiety of zinc selenite is generally of higher toxicological relevance than the zinc cations. Comparing the DNELs for the zinc/barium ion itself with the zinc/barium levels that are associated with the DNELs for barium/zinc selenite (based on selenite-data) indicated significantly higher values (in the range of factor 10 to 20) for the DNELs derived for the barium/zinc ion itself. Therefore, the subsequent assessment of the toxicity of barium/zinc selenite focuses on the selenium moiety.

 

In-vitro skin corrosion/irritation and in-vivo eye irritation testing has been performed since no reliable literature data were available on irritation properties of various Se-compounds.

 

Skin irritation:

In vitro studies were conducted with sodium selenate, sodium selenite and zinc selenite, using the human skin model EpiDermTM/ EpiSkinTM

Studies were conducted according to OECD guideline 439 to evaluate skin irritating effects. After the treatment with 25 mg of the solid test items sodium selenate or sodium selenite for 60 minutes, the relative absorbance values were reduced to 4.5% and 2.5%, respectively. This value is well below the threshold for irritation potential (50%). Therefore, both sodium selenate and sodium selenite are considered as irritant in the Human Skin Model Test. The relative adsorbance values for zinc selenite were reduced to 78.6%. This value is well above the threshold for irritancy (50%). Therefore this substance is not considered to possess an irritant potential. Zinc selenite has a significant lower solubility (compared to disodium selenate and disodium selenite), and it is therefore expected that the fraction dissolved selenite was too limited to cause any adverse irritating effects.

 

 In the second series of studies conducted according to OECD guideline 431 tissues of the human skin model EpiDerm™ were treated with 25 mg of the solid test items sodium selenate or sodium selenite for three minutes and one hour, respectively. After three minutes treatment with the test item, the relative absorbance values were reduced to 88.8% and 83.9%, respectively. This value is well above the threshold for corrosion potential (50 %). After one hour treatment, relative absorbance values were reduced to 79.2% and 55.4%, respectively. This value, too, is well above the threshold for corrosion potential (15%).

Therefore, both sodium selenate and sodium selenite are considered as not corrosive in the Human Skin Model Test.

  

Eye irritation:

An in vitro study was conducted according to OECD guideline 437 and EU method B.47, Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants.

Bovine corneas were used. The test items were incubated on the cornea for 4 hours at 32 ± 1 °C. Sodium selenate showed no effects on the cornea of the bovine eye, whereas sodium selenite showed mild effects on the cornea of the bovine eye. The calculated IVIS (in vitro irritancy score) for sodium selenate and sodium selenite were 0.133 and 11.616; respectively. Under the experimental conditions reported, the test item sodium selenate possesses no eye irritation potential, whereas sodium selenite possesses a mild eye irritation potential (according to ICCVAM).

According to OECD Guideline no. 437 (2013), a substance that induces an IVIS ≤3 does not require classification for eye irritation or serious eye damage (UN GHS No Category), whereas a substance that induces an IVIS ≥ 55.1 is defined as a corrosive or severe irritant.

 

The in vivo rabbit test (OECD 405) with zinc selenite showed conjunctival redness (grade 1) as well as secretion in all animals 1 hour after instillation. Chemosis was observed in one animal 1 hour after instillation. Corneae and the irises were not affected by instillation of zinc selenite. The fluorescein test performed 24 hours after instillation did not reveal any changes. There were no systemic intolerance reactions. Bases on these results and taking into account the classification criteria according to regulation (EC) No. 1272/2008, a classification for causing eye damage or eye irritation is not required for zinc selenite. This substance has a significant lower solubility (compared to disodium selenite), and it is therefore expected that the fraction dissolved selenite was too limited to cause any adverse irritating effects. 

 

Respiratory irritation:

Potential test item-related macroscopic findings were in the lungs were reported in the acute inhalation study with sodium selenate. In an acute toxicity study with zinc selenite (Leuschner, 2010) the gross pathological changes were recorded for each animal with particular attention to any changes in the respiratory tract. However, no abnormalities were detected at necropsy. As zinc selenite is not irritating to skin/eye, and shows no strong pH-effect upon dissolution in aqueous media, it is concluded that zinc selenite is no respiratory irritant.

 

 

Justification for classification or non-classification

Based on the available data, and taking into account the harmonised classifications, the following substance-specific classification is determined:

  

Disodium selenite:

Skin corrossion/irritation: Cat.2 - H315 - Causes skin irritation

Eye damage/irritation: Cat.2 - H319 - Causes serious eye irritation

 

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