Magnesium thiosulphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

no data available

Justification for type of information:

The basis for the read-across concept for this project is the equilibrium between sulfites, hydrogensulfites, and metabisulfites in aqueous solutions depending on pHvalue which is clearly described in published literature and summarised in the following equations:[1],[2]
           SO2+ H2O <->`H2SO3´         H2SO3<->H++ HSO3-<->2H++SO32-    2HSO3-<->H2O +S2O52-
As the nature of the cation should make no significant difference in this case concerning toxicity and solubility (all substances are very soluble in water), only the chemical and biological properties of the anion are considered relevant. Based on the described equilibrium correlations, we propose unrestricted read-across between the groups of sulfites, hydrogensulfites and metabisulfites.

Additionally, 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 added to the read-across concept.[2],[1]It is expected for this case that the substance is not stable enough under physiological conditions to fulfil the requirements of study guidelines and so the products of decomposition have to be considered.
       2 S2O42-+ H2O→2HSO3-+ S2O32 -
 
Not completely included in this read-across concept is the substance class of thiosulfates. Although thiosulfates may also disproportionate in aqueous solution to form polythionic acids and SO2(HSO3-), the required conditions are somewhat different (more acidic) and are therefore not strictly comparable with physiological conditions, except for the case of oral application where read-across should be considered unrestricted due to the strongly acidic conditions in the stomach:
       HS2O3-+ H2S2O3→HS3O3- + SO2+ H2O
Nevertheless, read-across for all other routes (dermal, inhalation) should also be considered.
The proposed read-across concept only applies to toxicological and ecotoxicological/environmental fate endpoints.
[1]Hollemann Wiberg, Lehrbuch der Anorganischen Chemie, 101.Auflage
[2]Handbook of Chemistry and Physics, Ed. Lide, DR, 88thedition, CRC Press

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Sulfur dioxide: Sulfite

Author:

Gunnison, A. F. & Benton, A.W.

Year:

1971

Bibliographic source:

Arch. Environ. Health, Vol. 22: 381 - 388.

Materials and methods

Objective of study:

other: disappearance from serum or plasma

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The hydrate of sulfur dioxide in mammalian plasma and serum was investigated. The longevity of sulfite in contact with mammalian plasma and known components of blood was investigated.
The reactivity of sulfite added to serum or plasma in vitro was followed by monitoring the concentration of the sulfite in the reaction mixture.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

sulfite

IUPAC Name:

sulfite

Details on test material:

- Name of test material (as cited in study report): Sulfite
- Analytical purity: reagent grade

Radiolabelling:

no

Test animals

Species:

human

Sex:

not specified

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Route of administration:

other: not applicable

Vehicle:

water

Details on exposure:

Plasma and serum samples were collected from an arm vein of adult humans with evacuated test tubes.
Edetate disodium at 2 mg/mL was used as an anticoagulant in the plasma samples.

Duration and frequency of treatment / exposure:

continuously until measurement (after 20 minutes)

Doses / concentrations

Remarks:

Doses / Concentrations:
1.7, 3.6 and 5.2 nanomols of sulfite

No. of animals per sex per dose / concentration:

not applicable

Control animals:

no

Positive control reference chemical:

No positive control substance was tested

Details on study design:

no data

Details on dosing and sampling:

Analysis of sulfite in presence of plasma or serum: To 200 µL of solution containing 40 µL of serum or plasma, approximately 6 microequivalents of hydrochloric acid, and quantities (up to 5.2 nM) of sulfite, 20 µL of PRA and 20 µL of formaldehyde reagent were added. A serum or plasma reagent blank was prepared. The optical density was measured against this blank after 20 minutes at 560 mµ.

in vitro reaction of sulfite with plasma or serum: Serum or plasma was incubated with a known amount of sulfite in a nitrogen atmosphere at 37°C, pH 7.4, using a ratio of 1 volume of serum (or plasma) to 1 volume of buffer and sulfite. These conditions are referred to as standard pH 7.4 incubation conditions. After incubation for the desired period of time, the amount of sulfite remaining in the mixture was analysed according the the procedure described above. This determination indirectly gives the amount of sulfite that "disappeared" from the incubation mixture and which was assumed to have reacted with the serum (or plasma).

Each analysis was replicated six times.

Statistics:

no data

Results and discussion

Preliminary studies:

no data

Main ADME results

Type:

other: disappearance from serum or plasma

Results:

Sulfite which enters the bloodstream during exposure of a mammal to atmospheric SO2 forms S-sulfonate groups with constituents of the plasma, probably exclusively by sulfitolysis of disulfide groups.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

no data

Details on distribution in tissues:

no data

Details on excretion:

no data

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

No details are given.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other:
The results give evidence that sulfite which enters the bloodstream during exposure of a mammal to atmospheric SO2 forms S-sulfonate groups with constituents of the plasma, probably exclusively by sulfitolysis of disulfide groups.
This interaction probably affords protection to many tissues of the body from the insult of high concentrations of sulfite.