Sodium selenite

Endpoint summary

Description of key information

Disodium selenite:

Acute oral toxicity: LD₅₀ of 7 mg/kg dw (Cummins and Kimura, 1971)

Acute inhalation toxicity: LC₅₀ (4 h) > 0.048 and ≤ 0.47 mg/L; MW conversion from disodium selenate to sodium selenite (LD₅₀ (4h) > 0.052 and ≤ of 0.51 mg Na₂SeO₄/L, Nagy, 2012)

Dermal toxicity: waived

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

7 mg/kg bw

Quality of whole database:

Literature data of good quality (Klimisch 2).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

0.052 mg/m³ air

Quality of whole database:

Read-across from GLP study of hight quality (Klimisch 1)

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

When no substance-specific data are available, 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 [Se^2-], 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 (SeO₃^2-). 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.

1. Acute toxicity – oral

 

Table 1 gives an overview of reliable acute oral toxicity studies for various Se-compounds. The table reports the test substance, test species, test result and reference.

 

Table 1: Acute oral toxicity of different Se-compounds: available data 

Test substance	Test Species	Result	Reference
Disodium selenite	rat	LD50: 7 mg/kg bw	Cummins and Kimura, 1971
Se-metal (powder)	rat	LD0: 5000 mg/kg bw	Prinsen, 1996a
Se-metal (crude)	rat	LD0: 5000 mg/kg bw	Prinsen, 1996b
SeO2	rat	LD50: 68.1 mg/kg bw	Sing and Junnarkar, 1991
SeO2	mice	LD50: 23.3 mg/kg bw	Sing and Junnarkar, 1991
Zn-selenite	rat	LD50: 50-500 mg/kg bw	Prinsen, 1996c

 

 

No data are available for disodium selenate. Information on fate and speciation of selenate in mammals shows that adsorbed selenate is rapidly transformed to selenide (via selenite as intermediate speciation form) which is the relevant form of Se in mammals; it is therefore expected that acute effects that are observed with sodium selenite are also relevant for disodium selenate. The data that were generated by Cummins and Kimura (1971) for disodium selenite can therefore be used for assessing the acute oral toxicity of disodium selenate.

Zinc selenite and Se-metal were significantly less toxic than disodium selenite. This is likely related to their lower solubility which is respectively 4 to 8 orders of magnitude lower than that of disodium selenite.

 

For BaSeO₃, the assessment entity approach is followed, and the acute oral toxicity of the selenite-fraction is considered similar to the toxicity of sodium selenite.  

 

  

2. Acute toxicity – inhalation

 

Table 2 gives an overview of reliable acute inhalation toxicity studies for various Se-compounds. The table reports the test substance, test species, test result and reference.

 

Table 2: Acute inhalation toxicity of different Se-compounds: available data 

Test substance	Test Species	Result	Reference
Disodium selenate	rat	LD50: 0.052 – 0.51 mg/L air	Nagy, 2012
Se-metal	rat	LD0: 5.67 mg/L air	Bennick, 1996
Zinc selenite	rat	LD50: 1 – 5 mg/L air	Leuchner, 2010

No data for: Disodium selenite, selenium dioxide

 

 

No data are available for disodium selenite. Information on fate and speciation of inorganic Se-species shows that selenate is rapidly transformed to selenide (via selenite as intermediate speciation form) which is the relevant form of Se in mammals; it is therefore expected that acute effects that are observed with tests that are conducted with disodium selenate, also take into account the effects that are caused by the common transformation products of selenate/selenite.

Selenite was also assessed in a test with zinc selenite. The observed acute toxicity was about one order of magnitude less than sodium selenate. This difference, however, can be explained by the lower solubility of zinc selenite (compared to sodium selenate). Based on this finding there is no indication that the acute toxicity (via inhalation) of selenite would be higher than the acute toxicity for selenate.

In addition, skin irritation tests with disodium selenate and disodium selenite show a similar response (Cat.2, based on OECD 439, no irritation based on OECD 431; see further), suggesting that both substances show a similar reaction with biological tissues.

 

No test data are available for selenium dioxide. Test data, however are not required if the substance is classified as corrosive. This is the case for selenium dioxide.

 

Justification for classification or non-classification

Selenium, disodium selenite and selenium compounds in general are subject to legally binding harmonised classifications. As included in the CLP Regulation (EC) No 1272/2008, Annex VI, Table 3.1, the following classifications with regard to acute toxicity are mandatory:

Selenium (Index-Nr 034 - 001 - 22 - 2):

Acute Tox. Cat.3 - H301 (oral)

Acute Tox. Cat.3 - H331 (inhalation)

Disodium selenite (Index-Nr 034 - 003 - 00 - 3)

Acute Tox. Cat.2 - H300 (oral)

Acute Tox. Cat.3 - H331 (inhalation)

Selenium compounds (general) (Index-Nr 034 - 002 - 00 - 8)

Acute Tox. Cat.3 - H301 (oral)

Acute Tox. Cat.3 - H331 (inhalation)

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

Disodium selenite:

Acute Tox. Cat.2 - H300 (oral)

Acute Tox. Cat.2 - H330 (inhalation) (more stringent than the harmonised classification for disodium selenite)