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EC number: 231-867-5
CAS number: 7772-98-7
A 3-generation chronic toxicity study (Til et al. 1972a) with treatment of rats (20 per sex and group) with dose levels of 0, 0.125, 0.25, 0.5, 1.0 or 2.0% Na2S2O5 administered in a 50 ppm thiamine-containing diet was identified as most reliable study for repeated dose toxicity and was defined as key study (read-across info, see `discussion`). Based on the read across concept for the group of sulfite and thiosulfate substances, this result is also applicable to sodium thiosulfate.
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
H2O <->`H2SO3´ H2SO3<->H++
the nature of the cation (i.e., sodium, potassium, ammonium…) is
not assumed to contribute substantially to differences in
toxicity and solubility (all substances 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
it is known that sodium dithionite disproportionates in water to
form sodium hydrogen sulfite and sodium thiosulfate (equation II),,
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
S2O42-+ H2O → 2HSO3-+
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
+ SO2+ H2O
Wiberg, Lehrbuch der Anorganischen Chemie, 101. Auflage
of Chemistry and Physics, Ed. Lide, DR, 88thedition,
and female rats received 0, 0.125, 0.25, 0.5, 1.0 or 2.0% Na2S2O5
in a thiamine-containing diet (50 ppm) for 104 weeks.
Based on the occurrence of occult blood in faeces and changes in
gastric morphology at dose levels of 0.5% or more, the NOAEL for
local chronic toxicity in this study is represented by the dose
of 0.25% metabisulfite (or 0.215% accounting for the loss of
metabisulfite). The corrected dose level corresponded to a dose
of 108 mg/kg bw/d Na2S2O5or an
equivalent dose of 180 mg/kg bw/day sodium thiosulfate.
Because there was no evidence of systemic toxicity following
chronic treatment, the NOAEL for systemic effects can be
expected above the highest dose of 2% sodium metabisulfite
corresponding to 955 mg/kg bw/d of Na2S2O5
or 1589 mg/kg bw/d sodium thiosulfate.
dose toxicity, dermal:
to regulation (EC) 1907/2006 Annex XI (weight of evidence),
testing for sub-chronic dermal toxicity is not considered to be
required, for the following reason: repeated dose toxicity study
via dermal route does not need to be performed since the
physico-chemical and toxicological properties do not suggest
potential for a significant rate of absorption through the skin
(for more information, refer to the section on toxicokinetics).
dose toxicity, inhalation:
to regulation (EC) 1907/2006 Annex XI (weight of evidence),
testing for sub-chronic inhalation toxicity is not considered to
be required, for the following reasons: iIn accordance with ECHA
guidance on information requirements and chemical safety
assessment-chapter R.8: characterisation of dose
[concentration]-response for human health, May 2008, a DNEL for
systemic effects can also be derived by route-to-route
extrapolation from a 90-day oral toxicity study in rats. Thus,
the calculated NOAEL of 1589 mg/kg bw/d sodium thiosulfate from
the chronic oral toxicity study with sodium metabisulfite was
used as the starting point for DNEL derivation.
it is neither scientifically nor justified due to animal welfare
reasons to initiate further inhalation toxicity studies.
dose toxicity, oral
effects in the stomach were the most predominant finding of repeated
dose toxicity: The NOAEL for local chronic effects in the study
described by Til et al. (1972) is represented by the dose of 0.25%
metabisulfite. The corrected dose level corresponded to a dose of 108
mg/kg bw/d Na2S2O5. All observed
effects (occurrence of occult blood in faeces and changes in gastric
morphology) were detected at higher dose levels at and above 0.5% in the
diet (220 mg/kg bw/d Na2S2O5). There
was no evidence of systemic toxicity following chronic treatment with
sodium metabisulfite. Therefore, the NOAEL for systemic effects can be
expected above the highest dose of 2% metabisulfite in the diet
corresponding to 955 mg/kg bw/d of Na2S2O5.
it can be concluded that based on the available animal data, Na2S2O5does
not have the potential to produce significant toxicity, or to be harmful
to humans, following repeated exposure at low or moderate exposure
concentrations relevant for classification. This
result can be read across to sodium thiosulfate without restriction. Thus,
the requirements for STOT-RE classification criteria according to
regulation (EC) 1272/2008 as specific target organ toxicant (STOT) –
repeated exposure, oral are not met, and no classification as specific
target organ toxicant is required.
dose toxicity, dermal
on physico-chemical properties of sodium metabisulfite and the
toxicokinetic behaviour (very limited penetration into the upper
epithelial layers of the epidermis,) there are no systemic risks to
humans with respect to dermal exposure to this substance.
may assume a conservative default of 1% for dermal absorption of sodium
metabisulfite, leading to the anticipation of a negligible toxicity via
the dermal route.
may be concluded that there will be no systemic risks to humans with
respect to dermal exposure to sodium metabisulfite, and no
classification for specific target organ toxicant (STOT) – repeated
exposure, dermal according to regulation (EC) 1272/2008 is required for
this substance or any suitable substance for read-across to this
dose toxicity, inhalation
to regulation (EC) 1272/2008, a classification for specific target organ
toxicity – repeated exposure shall be taken into account only when
reliable evidence associating repeated exposure to the substance with a
consistent and identifiable toxic effect demonstrates support for the
classification. However, there is no data or information available to
evaluate a potential for specific organ toxicity following repeated
inhalation exposure, and thus classification is not required.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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