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Description of key information

One in vivo skin irritation study with minor reliability (reliability 3) for ammonium thiosulfate (CAS 7783-18-8) is available and is used as supporting information based on the read-across approach within the group of thiosulfates. Read across from sodium sulfite (CAS 7757-83-7) provided one additional in-vivo skin irritation study that is used as key study and for classification. One in-vivo study on eye irritation for ammonium thiosulfate is available and is used for classification. All tests show a negative response, thussodium thiosulfate does not require classification either as skin or as eye irritant. 

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:
no adverse effect observed (not 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-

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

Skin irritation:

One in vivo study for sodium sulfite (CAS 7757-83-7), equivalent or similar to OECD 404, used for read-across is available (Grundler, 1981).

One supporting in vivo study (reliability 3) on dermal irritation of ammonium thiosulfate was identified which was conducted equivalent or similar

to OECD guideline 404 (Lemen, 1988). There was no erythema, oedema or any dermal effects noted at any time during the study. Based on the outcome of these studies and the proposed read-across approach, sodium thiosulfate is considered as not irritating to the skin.

Eye irritation:

One in-vivo study based on read-across to ammonium thiosulfate (CAS 7783 -18 -8), equivalent or similar to OECD guideline 405 is available (Lemen, 1988). All the animals exhibited excessive blinking/rubbing upon instillation of the test material and all the fluorescein examinations were negative at the 24-hour interval. No cornea opacity was observed in any of the animals during the study. Iritis (grade 1) was noted in one animal at the 1-hour interval only. Conjunctival redness (grade 1) was observed in all animals at the 1- and 24 hour intervals, then persisted in four animals at 48 hours. Chemosis (grade 2) was noted in four animals and grade 1 in two animals at the 1-hour interval and persisted as Grade 1 in two animals at 24 hours. Discharge Grade 1(any amount different from normal (does not include small amounts observed in inner canthus of normal animals)) or 2 (Discharge with moistening of the lids and hairs just adjacent to lids)) was noted in all the animals at the 1 hour interval only. Eye irritation in all the animals cleared by 72 hours.

Based on the outcome of the study and the proposed read-across approach, sodium thiosulfate is considered as not irritating to the eye.

Justification for classification or non-classification

Skin irritation:

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

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.

Based on the read-across approach (see `discussion`), it can be concluded that sodium thiosulfate has no skin irritating properties and thus has not to be classified as skin irritant according to Directive 67/548/EEC and subsequent regulations, and according to the EC Regulation No. 1272/2008 and subsequent regulations.

Eye irritation:

(for additional information, see `discussion´)

Read across reference Lemen (1988) is considered as key study and will be used for classification. The overall results are as follows:

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 = 0.33

Conjunctivae, 24, 48 and 72h after application: mean score = 0.66

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 = 0.66

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 = 0.33

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

Animal #4:

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 = 0.33

Animal #5:

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 = 0.66

Animal #6:

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 = 0.66

Mean eye irritation scores of all animals combined:

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 = 0.11

Conjunctivae, 24, 48 and 72h after application: mean score = 0.56

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 is not classified as eye irritant.

Based on the read-across approach within the group of thiosulfates, it can be concluded that sodium thiosulfate has no eye irritating properties and has not to be classified as eye irritant according to Directive 67/548/EEC and subsequent regulations, and according to the EC Regulation No. 1272/2008 and subsequent regulations.

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.