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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
This study report is a revised version of a study report from 1973. Minor deviations from the guideline without an effect on the results: - The stability of the test material was missing. -According to the guideline the observation period should be at least 14 day. In this study an observation period of 7 days was used. This is considered to have no effect on the results, since none of the animals died after 24 hours. - The clinical signs were documented group-wise and there was no statement about how many animals showed signs of toxicity. According to the guideline individual records should be held and number of animals showing toxic signs should be stated. - Body weight was not determined weekly and at death, which should be done according to the guideline. -There were no details about acclimatisation period, strain, individual body weights, diet, and environmental conditions. Also, it was not stated if animals were fasted prior to substance e administration or how often clinical examinations were made.
Justification for type of information:
Read-across
The basis for the read-across concept for this project is the equilibrium between sulfites, hydrogensulfites, and metabisulfites in aqueous solutions depending on pH value 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 compounds 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 -

All sulfite, hydrogensulfite and metabisulfite substances are highly soluble in water, establishing upon dissolution an equilibrium that depends on solution pH as follows: ,

1. SO2 + H2O <-> H2SO3
2. H2SO3 <-> H+ + HSO3- <-> 2H+ + SO32-
3. 2 HSO3- <-> H2O + S2O52-

Under oxidising conditions, e.g., in surface waters, sulfite is oxidized to sulfate catalytically by (air) oxygen or by microbial action. A half-life of 77 hour was measured in deionized water, already suggesting substantial abiotic degradation. However, the presence of metal cations in the environment, such as copper, iron and manganese, accelerates the oxidation rate. In soils, HSO3- and SO32- ions are unstable and quickly oxidise. Further, because of the instability of SO32-, metal sulfites are generally too soluble to persist in soils. Thus, the most stable and predominant sulfur form in freshwater and in all but highly reduced environments is sulfate (SO42-). In highly reduced soils and sediments, sulfites may be reduced to sulfides (Lindsay, 1979; OECD SIDS, 2012).

Only the properties of the sulfite anion are considered relevant determinants of environmental toxicity since respective cations, i.e. ammonium, calcium, magnesium, sodium and potassium, are not assumed to contribute substantially to differences therein. Sulfite, although naturally present in the environment and also a metabolite and intermediate of sulfur-containing amino acids in organisms, may have an impact on the environment at elevated levels. Sulfites do not bioaccumulate.

In sum, unrestricted read-across between the sulfites, hydrogensulfites and metabisulfites is justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
, "see rationale for reliability"
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Hydrosulfit konz. BASF (Sodium dithionite)

Test animals

Species:
rat
Strain:
other: not stated
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gassner rats
- Age at study initiation: young adult laboratory rats were used.
- Weight at study initiation: average weight at beginning of the test: 170 - 203 g






Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % CMC-solution (cleaned sodium carboxymethylcellulose) in doubly distilled water; Suspension
Details on oral exposure:
The doses were administered as aqueous suspensions of 2 %, 16 %, 20 % (2000 and 2500 mg/kg) and 30 % (3200 and 6400 mg/kg) test substance in 0.5 CMC-Solution (Hoechst AG).

MAXIMUM DOSE VOLUME APPLIED: The cocnetrations of the preparations were adjusted to achieve comparable volumes (about 10 -20 ml) per kg body weight.


Doses:
200, 1600, 2000, 2500, 3200 and 6400 mg/kg bw
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy performed: yes
- Examinations performed: group-wise documentation of clinical signs was performed over the 7-day study period. Body weight was determined before the start of the study for determination of dose.
Statistics:
On the basis of the observed lethality, the LD50 value was estimated or determined using a graphical evaluation of the dose response curve on probability paper.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 500 mg/kg bw
Based on:
test mat.
Mortality:
200 mg/kg bw: no deaths
1600 mg/kg bw: no deaths
2000 mg/kg bw: no deaths
2500 mg/kg bw: 3 males and 2 females died within the first 24 hours
3200 mg/kg bw: 4 males and 5 females died within the first 24 hours
6400 mg/kg bw: 5 males and 5 females died in the first hour.
Clinical signs:
6400 mg/kg bw: intermittent respiration, squatting posture and atony immediately after application.
3200 mg/kg bw: intermittent respiration, squatting posture and atony immediately after application. No clinical signs and findings in the surviving
animal from the first post observation day onward.
2500 mg/kg bw: intermittent respiration, squatting posture and atony immediately after application. No clinical signs and findings in the surviving animals from the forth post observation day onward.
2000 mg/kg bw: intermittent respiration, squatting posture and atony immediately after application. No clinical signs and findings in the surviving animals from the forth post observation day onward.
1600 and 200 mg/kg bw: no clinical signs and findings.
Body weight:
not stated
Gross pathology:
6400 and 3200 mg/kg bw: Congestive hyperemia, heart: dilation, stomach: dilatation, partly bloody ulcers and liquid content, intestine: hematinized, diarrheic content
2500 mg/kg bw: Congestive hyperemia, heart: dilatation, stomach: dilatation, liquid content, red discoloration of the glandular stomach, intestine: partly diffuse discoloration, diarrheic content
2000, 1600 and 200 mg/kg bw: Organs without particular findings.
Other findings:
not stated

Applicant's summary and conclusion

Interpretation of results:
not classified
Conclusions:
LD50 (male and female rats): approx. 2500 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.