Magnesium thiosulphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

2009-07-13 to 2009-07-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Guideline study reliable without restrictions Minor deviations without an effect on the results: - According to the guideline, the animals are observed at least once during the first 30 minutes after dosing, periodically during the first 24 hours (with special attention given during the first 4 hours), and daily thereafter, for a total of 14 days. In this study the animals were observed during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing. -According to the guideline, the rational for the starting dose should be stated. This was missing from the study report.

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

yes

Remarks:

, see "Rationale for reliability"

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Calcium thiosulphate

EC Number:

233-333-7

EC Name:

Calcium thiosulphate

Cas Number:

10124-41-1

Molecular formula:

CaS2O3

IUPAC Name:

calcium thiosulfate

Details on test material:

- Name of test material (as cited in study report): Aqueous solution of calcium thiosulfate (CaTS)
- Molecular formula: CaS2O3
- Physical state: Colourless, aqueous solution
- Composition of test material, percentage of components: Calcium thiosulfate : 23.7 %; Water: 76.3 %
- Lot No.: CaTS-Q6
- Expiration date of the lot: Not applicable
- Stability under test conditions: Test substance was expected to be stable for the duration of testing.
- Storage condition of test material: At room temperature
- pH: 6.5
- Solubility: Soluble in water
No further information on the test material was stated.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA
- Age at study initiation: 8 weeks
- Weight at study initiation: 164 - 186 grams
- Fasting period before study: Prior to each dosing, experimetnally naive rats were fasted overnight by removing the feed from their cages. During the fasting period, the rats were examined for health and weighed (initial). Feed was replaced approximately 3 -4 hours after dosing.
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent "Guide for the Care and USe of Laboratory Animals DHEW (NIH)". Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet: Purina Rodent Chow #5012
- Water (ad libitum): Filtered tap water
- Acclimation period: 6 - 10 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 23 °C
- Relative humidity: 56 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

An initial limit dose of 2000 mg/kg was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females sequentially received the same dose level.

MAXIMUM DOSE VOLUME APPLIED: Individual doses were calculated based on the intial body weights, taking into account the specific gravity (determined by EPSL) of the test substance. Dose volume: 0.26 - 0.30 ml
- Specific gravity: -1.243 g/ml

DOSAGE PREPARATION: The test substance was administered as received.
No further information on the oral exposure was stated.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights of the animals were recorded prior to test substance administration (initial) and again on Days 7 and 14 (termination) following dosing. The animals were observed for mortality, signs of gross toxicity, and behavioural changes during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.
- Necropsy of survivors performed: Yes, all rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
No further information on the study design was stated.

Statistics:

No data

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived.

Clinical signs:

There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behaviour. The rats appeared active and healthy during the study.

Body weight:

All animals gained body weight.

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Other findings:

No data

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute oral LD50 of Aqueous solution of calcium thiosulfate (CaTS) is greater than 2000 mg/kg bw in female rats.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as acute toxic via the oral route.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the oral route.