Sodium dithionite

Endpoint summary

Description of key information

Acute toxicity values (oral, dermal and inhalative) were determined for sodium dithionite utilizing substance specific data and data from read-across to sodium sulfite (CAS 7757-83-7).
Please see `discussion` below. 

Additional information

Read-across concept for sulfites, hydrogensulfites, metabisulfites, dithionites and thiosulfates:

A comprehensive read-across concept has been developed for sulfites, hydrogensulfites and metabisulfites, based on the pH-dependant equilibrium in aqueous solutions which is summarised in the following equations:^[1],[2]

           SO₂+ H₂O <->`H₂SO₃´         H₂SO₃<->H⁺+ HSO₃^-<->2H⁺+SO₃^2-    2HSO₃^-<->H₂O +S₂O₅^2-

Since the nature of the cation (i.e., sodium, potassium, ammonium…) is not assumed to contribute substantially to differences in toxicity and solubility (all compounds are very soluble in water), only the chemical and biological properties of the anion are considered as relevant determinants. Based on the described equilibrium correlations, unrestricted read-across between the groups of sulfites, hydrogensulfites and metabisulfites is considered justified.

 

Additionally, it is known that sodium dithionite disproportionates in water to form sodium hydrogen sulfite and sodium thiosulfate (equation II)^2,[1], so that this substance can also be considered to be covered by the read-across concept described above. Since it can easily be anticipated that the substance is not stable enough under physiological conditions to fulfil the requirements of study guidelines, instead the products of decomposition have to be considered:

 

       2 S₂O₄^2-+ H₂O→2HSO₃^-+ S₂O₃^2-

 

Not fully covered by this read-across concept is the substance class of thiosulfates: although the thiosulfates are also well known to disproportionate in aqueous solution to form polythionic acids and SO₂(HSO₃^-), this requires somewhat different, more acidic conditions. Therefore, read-across to sulfites is primarily restricted to appropriate physiological conditions, i.e. oral administration where the gastric passage with the strongly acidic conditions in the stomach will facilitate the chemical disproportionation described above:

 

       HS₂O₃^-+ H₂S₂O₃→HS₃O₃- + SO₂+ H₂O

 

[1]Hollemann Wiberg, Lehrbuch der Anorganischen Chemie, 101.Auflage

[2]Handbook of Chemistry and Physics, Ed. Lide, DR, 88^thedition, CRC Press

Acute toxicity oral:

One animal study for sodium dithionite on acute oral exposure is available (Gamer, 2003), conducted equivalent or similar to OECD guideline 401. The determined LD50 value (rats, males/females) was ca. 2500 mg/kg bw. Clinical signs at the dose level of 2500 mg/kg bw: intermittent respiration, squatting posture and atony immediately after application. No clinical signs and findings in the surviving animals from the forth post observation day onward.

Despite the `no-classification` result, the test item sodium dithionite is officially classified according to Directive 67/548/EEC (Xn: harmful if swallowed; R22) and according to EC Regulation No. 1272/2008 (Acute Tox. 4, H302).

Acute dermal toxicity:

One study on acute dermal toxicity, performed according to OECD 402 for the test item sodium sulfite (CAS 7757 -83 -7) is available. LD50 value was determined to be greater than 2000 mg/kg/bw (limit test).No systemic clinical signs were observed during clinical examination. No local effects were observed.

Acute inhalation toxicity:

One study equivalent or similar to OECD 403 for sodium sulfite (CAS 7757 -83 -7) has been performed which indicated a LC50 >5.5 mg/l (limit test). During exposure nothing abnormal was detected. After exposure: substance-contaminated heads, and unstable, staggering gait. After one day nothing abnormal was detected.

Justification for classification or non-classification

Acute oral toxicity:

The reference Gamer (2003) which indicates a LD50 value of ca. 2500 mg/kg bw, is considered as the key study for acute oral toxicity and will be used for classification.

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the oral route. According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the oral route.

Despite the `no-classification` result, the test item sodium dithionite is officially classified according to Directive 67/548/EEC (Xn: harmful if swallowed; R22) and according to EC Regulation No. 1272/2008 (Acute Tox. 4, H302).

Specific target organ toxicant (STOT) – single exposure: oral:

The classification criteria acc. to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 mg/kg bw. No classification required.

Acute dermal toxicity:

(for further information, please see `discussion`)

The referenceCords (2009) which indicates a LD50 > 2000 mg/kg bw, is considered as the key study for acute dermal toxicity and will be used for classification.

No systemic clinical signs were observed during clinical examination. No local effects were observed.

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the dermal route. According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the dermal route.

Based on the read-across concept, classification for sodium dithionite as acute toxic via dermal route is not anticipated.

Acute inhalation toxicity:

(for further information, please see `discussion`)

The reference Klimisch (1982) which indicates a LC50 value of > 5.5 mg/l, is considered as the key study for acute inhalation toxicity and will be used for classification.

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the inhalation route. According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.

Based on the read-across concept, classification for sodium dithionite as acute toxic via inhalation route is not anticipated.

Specific target organ toxicant (STOT) – single exposure: inhalation:

The classification criteria acc. to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, inhalation dust/mist/fume are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, inhalation dust/mist/fume for a Category 1 classification of 1.0 mg/L/4h and at the guidance value, inhalation dust/mist/fume for a Category 2 classification of 5.0 mg/L/4h. Therefore, no classification is required. Finally, any category 3 classification should primarily be based on human data. However, such classification is also not warranted, since only unspecific observations in test animals (mainly rats) were observed at artificially high inhalation exposure levels which are without relevance to current workplace conditions. It can be safely assumed that standard occupational hygiene measures provide a sufficient level of worker protection.