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Administrative data

Description of key information

Several reliable short-term repeated dose and sub-chronic studies are availble for the oral route:

  • Abdo (1994), NOAEL rat: 0.4 mg Se/kg bw/d (sub-chronic test with sodium selenite), NOAEL 0.4 mg Se/kg bw/d (sub-chronic test with sodium selenate)
  • Abdo (1994), NOAEL mouse: 0.9 mg Se/kg bw/d (sub-chronic test with sodium selenite), NOAEL 0.8 mg Se/kg bw/d (sub-chronic test with sodium selenate)
  • Bioulac (1992), NOAEL rat: 0.12 mg Se/kg bw/d (test with sodium selenite)
  • Johnson (2000), NOAEL mouse: 0.36 mg Se/kg bw/d (test with sodium selenite)

Based on these data, a NOAEL for rats of 0.4 mg Se/ kg bw/day has been selected as the key value for repeated dose toxicity via the oral route.

No studies on repeated dose toxicity via inhalation or dermal route are available.

Yang et al. (1989): NOAEL man: Se-intake of 850 µg Se/day per person; this figure is used as starting point for DNEL derivation (see chapter 5.11. of CSR).

It has to be emphasized, that the NOAEL according to Yang et al. (1989), which is used as starting point for DNEL derivation is based on human data. The existing studies on humans are considering a wealth of toxicological endpoints and overrule the available animal by far.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information


The ATSDR Toxicological Profile on Selenium (2003), which is currently the most comprehensive review, was used as key source of relevant data on selenium compounds because it contains a detailed evaluation of toxicity data, performed by a renowned scientific body. More recent reviews, e. g. the work conducted for the Canadian Soil Quality Guidelines / Sudbury Soil Study, were also been screened for additional data. The underlying assumption is that the key literature considered by renowned international organisations such as ATSDR has usually already been subjected to a reliability assessment.

Nevertheless, key references identified by ATSDR for selenates and selenites were re-evaluated and re-assessed for use in the REACH dossiers according to Klimisch and with respect to the requirements for risk assessment. Studies which were assessed as not adequate, not relevant or unreliable by expert judgement during the screening procedure were assigned to "disregarded study", and rated as "not reliable" (RL=3), data are not included as endpoint study record.

Evaluation of relevant references

Repeated dose toxicity, oral:

According to the evaluation criteria used by the experts of ATSDR (2003), a selection of studies on repeated dose oral toxicity with selenates and selenites providing reliable, quantitative estimates of No-Observed-Adverse-Effect Levels (NOAELs) or Lowest-Observed-Adverse-Effect Levels (LOAELs) are available (reported in ATSDR, 2003). All these references were obtained and re-evaluated according to the criteria of REACH. 

From the most reliable (RL=1) 90-day toxicity studies (Abdo, 1994: NTP technical report 38) with oral administration of sodium selenate and sodium selenite via drinking water conducted in Fischer rats and B6C3F1 mice it can be concluded that the rat is more sensitive than the mouse. Very little difference in toxicity of sodium selenate or sodium selenite was seen. Based on mortality, body weight depression, decreased water consumption and renal papillary lesions in rats, the lowest estimated no-observed-adverse-effect level (NOAEL) was 0.4 mg selenium/kg body weight per day for both selenate and selenite. For mice the NOAEL based on body weight depression and decreased water consumption can be established at 0.8 and 0.9 mg selenium/kg body weight per day for sodium selenate and sodium selenite, respectively. Results of these studies showed no differences in sensitivity to selenium between the sexes.

Two additional subchronic/subacute toxicity studies for sodium selenite are available with a special focus on hepatotoxicity in Sprague-Dawley rats (Bioulac 1992) and immunotoxicity in Balb/c mice (Johnson 2000). In the rat hepatotoxicity study, a somewhat lower NOAEL of 0.12 mg Se/kg bw/d was determined based on specific histopathological examinations of livers. However, this study was a dietary study and the difference of the resulting NOAEL to the key study NOAEL might result from the difference in routes of exposure and default calculation of dose levels based on amounts of test item in the diet. The NOAEL of 0.36 mg Se/kg bw/d obtained in the immunotoxicity study in mice with administration via drinking water is in the same range as the NOAEL for rats from the NTP study and somewhat lower than the NOAEL for effect of sodium selenite on mice from the NTP study (0.9 mg Se/kg bw/d).

For selenium a lot of human data is available. As laid down in the most recent publications of the German MAK commission (see chapter 5.11. of the CSR) the study of Yang et. al. (1989) revealed the most prominent effect of increased selenium levels in human serum. The results show that clinical signs (increased prothrombin time) may occur at a marginal blood-Se level of approximately ≥ 1 µg/mL or a corresponding marginal daily Se-intake of 850 µg Se/day.


Repeated dose toxicity, inhalation:

No data available.

Repeated dose toxicity, dermal:

No data available.

Justification for read-across:

The physico-chemical behavior of elemental Selenium (once it has formed an ion from its metal state), Sodium selenite, Sodium selenate and Selenium dioxide 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. This is also demonstrated by the results from the sub-chronic toxicity studies for sodium selenate and sodium selenite with rats and mice, indicating very little difference in toxicity of both substances.

Justification for classification or non-classification

Currently no substance-specific harmonised classification exists for sodium selenate. The substance is formally intrinsically included in a group entry named “selenium compounds with the exception of cadmium sulphoselenide and those specified elsewhere in this Annex“ and is therefore subject to harmonized classification according to Regulation (EC) No 1272/2008.

In the current version of Regulation (EC) No 1272/2008 (10th ATP) this substance group, in contrast to the specific entry for sodium selenite, is classified as STOT RE 2; H373**: May cause damage to organs through prolonged or repeated exposure (labelling: GHS08: Health Hazard depending on endpoint). This classification is obviously based on the previously existing classification R33 (based on DSD), even though there is no directly corresponding classification to R33 in Regulation (EC) No 1272/2008. In a weight of evidence approach the following aspects should be considered:

(i) According to Regulation (EC) No 1272/2008 classification in Category 2 is applicable, when significant toxic effects observed in a 90-day repeated-dose study conducted in experimental animals are seen to occur within the guidance value ranges of 10 < effect level < 100 mg/kg bw/d. However, although for sodium selenite and sodium selenate some single incidences of liver toxicity or renal findings were observed in studies with laboratory animals, these cannot be regarded as significant health effects for humans, because they are not consistently observed in various studies.

(ii) In addition, information and results of data presented in the peer-reviewed ATSDR (2003) publication is included in the weight of evidence approach. It is stated that in many aspects, similar patterns of toxicity have been reported for selenium in human and animal systems.“However, species-specific differences in toxicity are present (e. g., the main effect of selenium toxicity in rodents is damage to the liver, which is not observed in humans) and this may represent evidence of underlying differences in how selenium is metabolized. [... ] The lack of evidence of liver damage in humans due to selenosis, despite the animal data to the contrary, suggests a problem with the animal models of the disease.

According to the weight-of-evidence approach above, no classification would be appropriate for specific target organ toxicity of sodium selenate.


Nevertheless the legal binding classification is applied.