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Description of key information

Read across from potassium sulfite and sodium sulfite as well as ammonium-, sodium- and potassium hydrogensulfite provided five reliable in-vivo skin irritation studies.  
The tests on skin irritation show a negative response, thus, based on read-across (see `discussion`), sodium dithionite does not require classification as skin irritant.
The results of two reliable eye irritation studies for the test item sodium dithionite indicate eye irritation properties. According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item should be classified as eye irritant. According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item should be classified as eye irritant Category 2.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

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++SO32-   2HSO3-<->H2O +S2O52-

In consequence, under most physiological circumstances, sulfite and hydrogensulfite anions will be present in almost equimolar quantities, irrespective of their origin either as sulfites, hydrogensulfites and metabisulfites. Unrestricted read-across between the groups of sulfites, hydrogensulfites and metabisulfites is therefore considered justified. Since the nature of the cations such as sodium, potassium and 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 anionic sulfite moiety are considered as relevant determinants.

Further, it is well established that sodium dithionite is unstable in water, thereby disproportionating to form sodium hydrogen sulfite and sodium thiosulfate (equation II)[1], so that this substance is also considered to be covered by the read-across concept described above. Since the substance is not stable enough under physiological conditions to fulfil the requirements of most HH test guidelines, instead the products of decomposition have to be considered:

      2 S2O42-+ H2O→2HSO3-+ S2O32-

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

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

Like all “sulfite substances”, the dithionite anion has strongly reducing properties and decomposes/disproportionates rapidly in aqueous media (especially under acidic anaerobic conditions) to form sulfite and thiosulfate (S2O32-); under aerobic conditions, it will additionally be oxidised to finally form sulfate as the final oxiodation/decomposition product. According to Hofmann and Rüdorff (1969) and Holleman and Wiberg (1995), this process can roughly be described by the following equations (under aerobic conditions and at low concentrations, reaction (2) is favoured:

 

2 Na2S2O4+ H2ONa2S2O3+ 2 NaHSO3(anaerobic conditions) (1), as described above

 

Na2S2O4+ O2+ H2ONaHSO4+ NaHSO3(aerobic conditions) (2)

 

According to the literature overview of Münchow (1992) the following principal decomposition patterns can be described for dithionite in relation to pH ranges at temperatures between 0°C and 32°C for 0.0025 molar solutions:

 

strongly alkaline medium: 3 S2O42-+ 6 OH-5 SO32-+ S2-+ 3H2O

weakly alkaline to weakly acidic medium: 2 S2O42-+ H2O2 HSO3-+ S2O32-

acidic medium: 2 H2S2O43 SO2+ S + 2 H2O

strongly acidic medium: 3 H2S2O45 SO2+ H2S + 2 H2O  

With limitations, this read-across concept also extends to 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 more acidic conditions. Therefore, read-across to sulfites is primarily restricted to corresponding physiological conditions such as oral administration where the gastric passage with the strongly acidic conditions in the stomach will facilitate the chemical disproportionation described below:

      HS2O3-+ H2S2O3→HS3O3-+ SO2+ H2O

 

Skin irritation:

Skin irritation data specifically for sodium dithionite are not available, which is why read-across to similar substances (sodium and potassium sulfite as well as ammonium, sodium and potassium hydrogensulfite) is made.One in vivo study (Kirsch, 1989) on dermal irritation of potassium sulfite was identified which was conducted according to OECD guideline 404. The test read-across test item showed no skin irritating properties. No erythema or oedema were seen in any of the rabbits at 24, 48, 72 hours after the beginning of the study. Very slight erythema was observed in two animals at the 4-hour reading, which had disappeared at the 24 hour reading.

One further in-vivo study for the read-across substance sodium sulfite (Grundler, 1981) equivalent or similar to OECD 404, used for read-across is available. No skin irritating properties of sodium sulfite could be determined.

Three study reports equivalent or similar to OECD 404, prepared by Consonni (2004) for the substances ammonium hydrogensulfite, sodium hydrogensulfite and potassium hydrogensulfite indicated no irritation properties when applied as aqueous solution (70%, 40% and 32%; substances as such are not existent in dry form). Erythema and edema scores were zero after 24, 48 and 72h for all substances.

Another in vivo study on dermal irritation of ammonium thiosulfate is merely of supportive nature (reliability 3) (Lemen, 1988). There were either only mild signs of erythema, oedema or other dermal effects in both studies, or none at all. Based on the outcome of the above mentioned studies and the proposed read-across approach, sodium dithionite is considered as not irritating to the skin.

For the transformation product “thiosulfte”, only an unreliable (reliability 3) in vivo skin irritation study but with a negative outcome for ammonium thiosulfate (CAS 7783-18-8) is available and is therefore used as supporting information. Based on read-across from sodium sulfite (CAS 7757-83-7), ammonium thiosulfate does not require classification as a skin irritant.

 

Eye irritation:

Two in-vivo studies, according to OECD guideline 405specificallyfor sodium dithionite are availablewhich is why read-across was not considered to be required.One study (Remmele, 2006) indicated that sodium dithionite is not irritating to the eye. Moderate or severe conjunctival redness (grade 2 or 3) were noted in the animals from 1 hour up to 72 hours after application. Slight or moderate conjunctival chemosis (grade 1 or 2) were noted in all animals 1 hour after application. Slight conjunctival chemosis, observed in two animals after 24 and 48 hours, persisted in one animal up to 72 hours. Slight or moderate discharge (grade 1 or 2) was noted in all animals 1 hour after application, only. Additionally, injected scleral vessels in a circumscribed area or circular were noted in all animals up to 24 hours after application. The ocular reactions were reversible in all animals within 7 days after application.

The study Kaufmann (2003) indicates that sodium dithionite has eye irritating properties. Moderate or severe conjunctival redness (grade 2 or 3), moderate conjunctival chemosis (grade 2) and slight discharge (grade 1) were observed in all animals 1 hour after application. Severe conjunctival redness, observed in all animals at the 24-hour reading, persisted in two animals up to 48 hours and decreased to moderate 72 hours after application. In the other animal severe conjunctival redness decreased to slight (grade 1) 7 days after application. Moderate conjunctival chemosis decreased in two animals to slight (grade 1) 24 hours after application and was seen in one of these animals up to the 72-hour reading. The third animal exhibited moderate conjunctival chemosis at 24 hours which diminished to slight 48 hours after application. Additionally, circular injected scleral vessels were noted in all animals 1 hour after application, which reduced to a circumscribed area at the 24-hour reading in all animals and persisted up to 48 hours in one animal and up to 72 hours in the other two animals. Moreover, one animal showed a white discoloration at the nictitating membrane 48 and 72 hours after application. The ocular reactions were reversible in two animals within 7 days and in one animal within 14 days after appplication.

For the transformation product (ammonium) thiosulfate, a study with negative outcome is available, thereby substantiating the conclusion that sodium dithionate does not qualify as an eye irritant.


Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation:

(for additional information, see `discussion´)

References Kirsch, J. (1989) and Grundler, O.J. (1981) are considered as key studies for skin irritation and will be used for classification. The overall irritation results are as follows:

Read-across: Kirsch, J. (1989):

Erythema, edema, 24, 48, 72h after application: max score = 0

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as skin irritant. According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as skin irritant.

 

Read-across: Grundler, O.J. (1981):

(for additional information, see `discussion´)

Erythema, 24, 48, 72h after application: max score =1, mean score = 0.33.

Edema, 24, 48, 72h after application: max score = 0

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as skin irritant. According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as skin irritant.

 

Read-across: Consonni (2004):

Three study reports equivalent or similar to OECD 404, prepared by Consonni (2004) for the substances ammonium hydrogensulfite, sodium hydrogensulfite and potassium hydrogensulfite indicated no irritation properties when applied as aqueous solution (70%, 40% and 32%; substances as such are not existent in dry form). Erythema and edema scores were zero after 24, 48 and 72h for all substances.

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test items are not classified as skin irritant. According to the EC Regulation No. 1272/2008 and subsequent regulations, the test items are not classified as skin irritant.

Based on the outcome of the read-across studies, it can be concluded, that sodium dithionite is not irritating to the skin and has not to be classified according to the criteria specified by Directive 67/548/EEC and subsequent regulations and according to the EC Regulation No. 1272/2008 and subsequent regulations.

Eye irritation:

The references Remmele (2006) and Kaufmann (2003) are considered as key studies and will be used for classification.The overall results are as follows:

Remmele (2006):

Animal #1:

Corneal opacity: mean score, 24, 48 and 72h after application = 0

Iris: mean score, 24, 48 and 72h after application = 0

Chemosis: mean score, 24, 48 and 72h after application = 1

Conjunctivae, 24, 48 and 72h after application: mean score = 2

Animal #2:

Corneal opacity: mean score, 24, 48 and 72h after application = 0

Iris: mean score, 24, 48 and 72h after application =0

Chemosis: mean score, 24, 48 and 72h after application = 0

Conjunctivae, 24, 48 and 72h after application: mean score = 2.67

Animal #3:

Corneal opacity: mean score, 24, 48 and 72h after application = 0

Iris: mean score, 24, 48 and 72h after application = 0

Chemosis: mean score, 24, 48 and 72h after application = 0.67

Conjunctivae, 24, 48 and 72h after application: mean score = 2

 

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as eye irritant . According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item should be classified as eye irritant (Eye Dam.2, H319).

Kaufmann (2003):

Animal #1:

Corneal opacity: mean score, 24, 48 and 72h after application = 0

Iris: mean score, 24, 48 and 72h after application = 0

Chemosis: mean score, 24, 48 and 72h after application = 1

Conjunctivae, 24, 48 and 72h after application: mean score = 2.67

Animal #2:

Corneal opacity: mean score, 24, 48 and 72h after application = 0

Iris: mean score, 24, 48 and 72h after application =0

Chemosis: mean score, 24, 48 and 72h after application = 0.33

Conjunctivae, 24, 48 and 72h after application: mean score = 2.67

Animal #3:

Corneal opacity: mean score, 24, 48 and 72h after application = 0

Iris: mean score, 24, 48 and 72h after application = 0

Chemosis: mean score, 24, 48 and 72h after application = 1

Conjunctivae, 24, 48 and 72h after application: mean score = 3

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item should be classified as eye irritant (R36). According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item should be classified as eye irritant (Eye Dam.2, H319).

 

Respiratory irritation:

The classification as respiratory irritant is covered under the endpoint specific target organ toxicity- single exposure and repeated exposure. Please refer to the endpoint summaries on acute toxicity (endpoint 7.2) and repeated dose toxicity (endpoint 7.5) for further information.