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Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Reliable data are available from two LLNA studies with the read-across substances sodium selenite and zinc selenite.

It should be noted that the following factors do need special attention for adequate interpretation of the study results: ·

(1) The substance Zinc selenite (water solubility is 16 mg/L) is devoid of any potency for skin senitization as has been recently shown in reliable LLNA testing even though the applied method by measurements of the weights of the lymph nodes and cell counts has not been officially evaluated.

(2) The substance Sodium selenite is dermally relatively toxic (one animal died at a test concentration of 1.0 mg/L and testing for skin irritation has shown that it is a significant skin irritant, i.e. Sodium selenite may lead to “hyperreactivity” and be a ”non-specific stimulis” (as has been described by Basketter et al. (1998) [1] for “difficult” substances).

(3) “Non-specific cell activation as a result of inflammatory processes” is discussed by Ulker et al. (2011) [2] as a possible confounding factor for a false positive result. “Ear weight determination” is described by Ehling et al. (2005) [3] for the identification of “skin irritation properties of the test item” in LLNA. The effect on ear weights as observed in the preliminary range finding study with Sodium selenite has shown a clear correlation of test concentrations with the SI, i.e. observation of the borderline SI of 3.2 occured at clearly elevated ear weights (even though these were within the range of historical controls according to the study author).

(4) Test results of the highly water soluble substance Sodium selenite (water solubility is 898 g/L) indicate that the SI is of only a (very) borderline nature (2 times clearly below 3 and only one time slightly above 3) and the resulting concentration-response curve is not clearly positive (medium concentration reveals SI below the lowest concentration). Slightly positive SI at 0.5 % may have been only observed due to proximity to “toxic” concentration(s) because one animal died at a concentration of 1.0 %, i.e. the concentration-response curve may be incompatible with an unbiased biological response (as has been commented by Chamberlain et al. (1996) [4]).

(5) Selenium is an essential element (micronutrient) for animals and humans, therefore its sensitizing potential is difficult to establish per se as has been shown by the respective results for Copper chloride: Also Copper is essential for mammalian cells and it could be shown that it was positive in the LLNA whereas it was negative in the Guinea Pig Maximisation Test (GPMT) and in the Buehler Assay both with rabbits (as has been reported in summarizing format by Basketter et al. (1996) [5]). Also the resulting SIs (even though in general even higher than for Selenium selenite) were very comparable as observed with Selenium selenite.

Taking together these experimental results from (2) to (5) indicate for strong evidence that the very water soluble substance Sodium selenite is not a significant skin sensitizing agent, but obviously the LLNA seems to give a false positive result due to several (confounding) factors (for recent review of these factors see also Anderson et al. (2011) [6]).

Justification for read-across:

Due to the facts, that

  • the poorly water soluble substance Zinc selenite is devoid of any skin sensitizing potency, and
  • the highly water soluble substance Sodium selenite (solubility 898 g/L) also has to be regarded of being devoid of any significant skin sensitizing potency, and
  • 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-] takes place which is the single common precursor for its further metabolic conversion (Ohta and Suzuki (2008) [8])

it is concluded that neither elemental Selenium (which is only of extremely low water solubility of max. 3.77 μg/L), nor Sodium hydrogenselenite (solubility 1012.7 g/L), Barium selenite (solubility 66.65 mg/L), Sodium selenate (solubility 585 g/L) and Selenium dioxide (solubility 1353 g/L) do need to be classified (and labelled accordingly) for skin sensitization because there is no evidence to assume that the various Selenium moieties will behave differently from the tested substances Sodium selenite and Zinc senite.

References:

[1] Basketter, D.A. et al. (1998): Strategies for identifying false positive responses in predictive skin sensitization tests, Food and Chemical Toxicology 36, 327-333

[2] Ulker, O.C. et al. (2011): Evaluation of auricular lymph node cell lymphocyte proliferation and cytokine production as non-radioactive endpoints during murine contact allergy, J Immunotoxicol. 2011 Jun 8(2):131-9, available at: doi: 10.3109/1547691X.2010.547996

[3] Ehling, G. et al. (2005): An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: 2nd round, Toxicology 15, 212(1), 69-79

[4] Chamberlain et al. (1996): The local lymph node assay: Status of validation, Food and Chemical Toxicology 34, 999-1002

[5] Basketter, D.A. et al. (1996): The local lymph node assay: A viable alternative to currently accepted skin sensitization tests, Food and Chemical Toxicology 34, 985-997 [6] Andersen, E. et al. (2011): The LLNA: A brief review of recent advances and limitations, Journal of Allergy 2011, available at: doi:10.1155/2011/424203

[6] Andersen, E. et al. (2011): The LLNA: A brief review of recent advances and limitations, Journal

of Allergy 2011, available at: doi:10.1155/2011/424203

[7] Senff, H. et al. (1988): Allergic contact dermatitis from selenite, Contact Dermatitis 19/1, 73-74

[8] Ohta, Y. and Suzuki, K.T. (2008): Methylation and demethylation of intermediates selenide and methylselenol in the metabolism of selenium. Toxicology and Applied Pharmacology 226, 169- 177


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Conclusion for classification of Sodium selenate

Additionally to the data from experimental animals human data needs to be taken into account. To that end the recently published documentation on the German OEL (Occupational Exposure Limit: see German MAK Commission: Toxikologisch-arbeitsmedizinische Begründungen von MAK-Werten “Selen und seine anorganischen Verbindungen”, 2011, available at: http://onlinelibrary.wiley.com/book/10.1002/3527600418) has shown that only two reports with regard to potentially acquired skin sensitization in humans (workers) are available, which both do not sufficiently indicate for an allergenic potency for Selenium in humans because these reports do not allow for an adequate distinction from unspecific or toxic dermal reactivity. In particular it is reported that a laboratory technician was tested positive in an epicutaneous assay with a 0.1 % Sodium selenite solution but negative in intracutaneously and also no positive reaction could be elicitated in 15 control persons (Senff et al. (1988) Allergic contact dermatitis from selenite, Contact Dermatitis 19/1, 73-74).

From these results the MAK Commission derives the conclusion that for Selenium and its inorganic compounds no assignment with "Sa" (potency for sensitization of airways) nor "Sh" (potency for sensitization of skin) should follow.

Due to the facts, that

  • the poorly water soluble substance Zinc selenite is devoid of any skin sensitizing potency, and
  • the highly water soluble substance Sodium selenite (solubility 898 g/L) also has to be regarded of being devoid of any significant skin sensitizing potency, and
  • 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-] takes place which is the single common precursor for its further metabolic conversion (Ohta and Suzuki (2008) Methylation and demethylation of intermediates selenide and methylselenol in the metabolism of selenium. Toxicology and Applied Pharmacology 226, 169- 177)

it is concluded that neither elemental Selenium (which is only of extremely low water solubility of max. 3.77 μg/L), nor Sodium hydrogenselenite (solubility 1012.7 g/L), Barium selenite (solubility 66.65 mg/L), Sodium selenate (solubility 585 g/L) and Selenium dioxide (solubility 1353 g/L) do need to be classified (and labelled accordingly) for skin sensitization because there is no evidence to assume that the various Selenium moieties will behave differently from the tested substances Sodium selenite and Zinc senite.

In summary when applying a weight of evidence approach it is therefore concluded that Sodium selenate would not need to be classified for skin sensitization.