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Description of key information

Read across from potassium sulfite (CAS 10117-38-1) and sodium sulfite (CAS 7757-83-7) provided two reliable in-vivo skin irritation studies.  One in-vivo study on eye irritation for potassium metabisulfite is available. 
The tests on skin irritation show a negative response, thus potassium metabisulfite does not require classification as skin irritant.
The results of the eye irritation study indicate eye irritation properties for the substance potassium metabisulfite. According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item should be classified as as a serious eye irritant (Xi, R41). According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item should be classified as a serious eye irritant (Eye Dam.1, H318).

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-

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 (Kirsch, 1989) on dermal irritation of potassium sulfite was identified which was conducted according to OECD guideline 404. The 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 sodium sulfite (CAS 7757-83-7) equivalent or similar to OECD 404, used for read-across is available. No skin irritating properties of sodium sulfite could be determined.

One supporting study (Zeller & Hofmann, 1974; reliability 3) for the test substance potassium metabisulfite could be identified. Although one animal exposed for 20 h showed marginal erythema at 24 h and desquamation at the end of the 8 day observation period, the other animal showed no signs of irritation. In addition to the extended lenght of application, these data were not sufficient for classification as irritant to skin.

Eye irritation:

One in-vivo study, equivalent or similar to OECD guideline 405 is available (Kieczka, 1984). During the 1-hour reading slight corneal opacity was seen in one animal. Also, at the 1-hour reading well-defined conjunctival redness and severe chemosis were observed in all animals. Detachment of the cornea and discharge of blood were observed in one male at the 1-hour reading. At the 24-hour reading suppuration in two animals was observed. At the 48 hour reading suppuration was observed in all animals. At the 72 hour reading suppuration was observed in one male and suppuration, small retractions in the eyelids, and pupil contration were observed in one female. On day 8, the corneal opacitiy worsened in all animals. The conjunctival redness (well-defined) remained the same throughout the observation period, except for one animal in which slight conjunctival redness was observed on day 8. The chemosis was not fully reversed in any of the animals on day 8, but became better. On day 8 marginal vascularization of the cornea and small retractions in the eyelids were observed in one female. In addition, marginal vascularization of the cornea was observed in the male rabbit. Furthermore, marginal vascularization of the cornea, small retractions in the eyelids, suppuration, and pupil contration were observed in the remaining female


Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin irritation:

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):

(for additional information, see `discussion´)

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.

Based on the outcome of the read-across studies, it can be concluded, that potassium metabisulfite 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 reference Kieczka (1984) 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 = 0.67

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

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

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

Animal #2:

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

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

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

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

Animal #3:

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

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

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

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 should be classified as a serious eye irritant (Xi, R41). According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item should be classified as a serious eye irritant (Eye Dam.1, H318).

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.