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Description of key information

Acute toxicity values (oral, dermal and inhalative) were determined for sodium thiosulfate utilising data from read-across to sodium sulfite (CAS 7757-83-7), potassium thiosulfate (CAS 10294-66-3) and calcium thiosulfate (10124-41-1)
Please see discussion below.

Key value for chemical safety assessment

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-

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 S2O42-+ H2O→2HSO3-+ S2O32-

 

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-+ H2S2O3HS3O3- + SO2+ H2O

 

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

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

Acute toxicity oral:

Three animal studies on acute oral exposure are available, conducted equivalent or similar to OECD guideline 401 or according to OECD 425.One study (Douds, 1996) indicates a LD50 value of >2500 mg/kg/bw (male and female rats) for the test item potassium thiosulfate (CAS 10294 -66 -3). One OECD 425 study (Durando, 2009) performed with calcium thiosulfate (CAS 10124 -41 -1) as test item indicated a LD50 >2000 mg/kg/bw (femal rats) and a supporting study (Lemen, 1988, reliability 3) performed with ammonium thiosulfate (CAS 7783 -18 -8) resulted in a LD50 value of about 3800 mg/kg/bw.

Acute dermal toxicity:

One study on acute dermal toxicity, performed according to OECD 402 for the test item potassium thiosulfate (7783 -18 -8) is available. LD50 value was determined to be greater than 2000 mg/kg/bw (limit test).The most notable clinical abnormalities observed during the study included transient incidences of fecal stain. Dermal irritation was noted at the sites of test article application.One supporting study (reliability 3) according to OECD 402 for the test item ammonium thiosulafte is available with a determined LD50 value of >2000 mg/kg bw.Clinical observations of all animals were normal for the 14-day observation period. Skin reactions were only observable on Day 1 and Day 3. On Day 1, erythema was observed in all the females and three of the males with one male exhibiting well-defined erythema. Very slight oedema was observed in one male only on Day 1. On Day 3, very slight erythema was observed in four animals. There were no other dermal effects observed in any of the animals.

Acute inhalation toxicity:

One study (Douds, 1996) equivalent or similar to OECD 403 for potassium thiosulfate (10294 -66 -3) has been performed which indicated a LC50 >2.6 mg/l (limit test). The most notable clinical abnormalities observed durng the study included rales, salivation, urine stain, rough haircoat and dark material around the facial area, as well as scab(s) and hair loss.

One study (Klimisch, 1982) 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). Read-across to this substance is considered justified because of particle size considerations, based upon which the bulk of inhaled material would be translocated to the gut, so that the gastric passage will transform thiosulfate to sulfite, and since any toxicity may safely be expected to be of only systemic nature because of the absence of any local effects for this substance. 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:

(for further information, please see `discussion`)

The references Douds (1996) which indicates a LD50 value of ca. 2500 mg/kg bw, and Durando (2009) with a determined LD50 of >2000 mg/kg bw are considered as key studies for acute oral toxicity and will be used for classification.

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

Based on the read-across concept, classification for sodium thiosulfate as acute toxic via oral route is not required.

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 reference Douds (1996) which indicates a LD50 > 2000 mg/kg bw, is considered as the key study for acute dermal toxicity and will be used for classification.

The most notable clinical abnormalities observed during the study included transient incidences of fecal stain. Dermal irritation was noted at the sites of test article application.

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 of sodium thiosulfate as acute toxic via dermal route is not required.

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 of sodium thiosulfate as acute toxic via inhalation route is not required.

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.