Dipotassium disulphate

Endpoint summary

Description of key information

Oral (based on read across to H2SO4 with correction for molecular weight differences): similar to OECD 401; rat LD50: 5547 mg/kg. Reliability = 2
Inhalation (based on read across to H2SO4 with correction for molecular weight differences): similar to OECD 403; rat 4-hr LC50: 972 mg/m3. Reliability =2 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Remarks:

The study was conducted according to the guideline in effect dated 2001.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

other: Carworth-Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4-5 weeks of age
- Weight at study initiation: 90-120 grams
- Fasting period before study: no

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.250 g/mL

Doses:

- The doses were arranged in a logarithmic series differing by a factor of two.
- Concentration in vehicle: 0.250 g/mL

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Sex:

male

Dose descriptor:

LD50

Effect level:

2 140 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 1540-2990 mg/kg

Conclusions:

This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
LD50 = 2140 mg/kg

Executive summary:

An acute oral toxicity study with the test substance on groups of 5 rats reported an LD₅₀ of 2140 mg/kg/body weight.

Endpoint conclusion

Dose descriptor:

LD50

Value:

5 547 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Animals observed for 21 days

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6-7 weeks

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: humid air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 27-inch Rochester-type chronic exposure chamber
- Method of holding animals in test chamber: individual cages
- System of generating particulates/aerosols: mixing SO3 with humid air to produce H2SO4 droplets
- Source and rate of air: 10 cfm
- Temperature, humidity, pressure in air chamber: 40% humidity; temperature and pressure not reported

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter): 1.1 - 2.2 µm

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

>= 1 - <= 8 h

Remarks on duration:

selected exposure times were 1, 2, 4 and 8 hours for each concentration

Concentrations:

240, 470, 730, 800, 1080 and 1090 mg/m³

No. of animals per sex per dose:

8

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology; Animals dying spontaneously and sacrificed animals were necropsied. The time of death was noted, and the lung, trachea, stomach and turbinates were removed, fixed in 10% formalin and processed for histologic examination using standard procedures.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 375 mg/m³ air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Mortality was 0, 63, 63, 75, 63 and 88% after 4-hour exposure to 240, 470, 730, 800, 1090 and 1080 mg/m³, respectively.
The majority of rats died during the 2 weeks after exposure. Exceptions to this were early deaths which occurred when rats were exposed to H2SO4 concentrations above 700 mg/m3 for 4 to 8 hours.

Gross pathology:

Examination of rat tissues revealed ulceration of turbinates, trachea and larynx in animals dying during exposure or shortly thereafter. Lesions noted in rats dying 1-2 weeks after exposure included fibrosis of the larynx and bronchopneumonia associated with aspirated foreign material.

Other findings:

Rats showed increased mortality with increased concentration. This appeared more dramatically in mice than in rats during the first 24 hours. The fact that deaths occurred within 24 hours in the mouse group exposed for 1 and 2 hours and not in the rat group may be interpreted as an indication of greater sensitivity in the mouse. When total deaths in 21 days were considered, however, the rat appeared to exhibit increased sensitivity with increased H2S04 concentration as did the mouse. In fact, rat mortality increased more rapidly with increased concentration than mouse mortality. No deep lung lesions were noted in rats that could be attributed to direct test substance insult. Animals died from upper respiratory tract lesions before test substance aerosol concentrations affected the deep lung.

Interpretation of results:

moderately toxic

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
LC50 was approximately 375 mg/m³ for rats.

Executive summary:

Rats (Fischer-344) were exposed to various concentrations of test substance aerosols for 1 to 8 hours. Mortality and histologic changes resulting from these exposures were determined. Mortality in the majority of rats occurred 1-2 weeks following exposure, the exception being early deaths resulting from very high aerosol concentrations. Examination of tissues revealed ulceration of the turbinate, trachea and larynx in rats dying during exposure or shortly thereafter. Lesions noted in rats dying 1-2 weeks after exposure included bronchopneumonia associated with aspirated foreign material. No deep lung lesions were noted in rats that could be attributed to direct test substance insult. Animals died from upper respiratory tract lesions before test substance aerosol concentrations affected the deep lung. The LC₅₀ for rats was approximately 375 mg/m³.

Endpoint conclusion

Dose descriptor:

LC50

Value:

972 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No data were available for acute oral, dermal, or inhalation toxicity with the test substance, but oral LD₅₀ and inhalation LC₅₀ studies in rats with H₂SO₄ were used as a read across to fulfil the data gap for the test substance. The underlying hypothesis for the read-across between the test substance and H₂SO₄ is the likelihood of common precursors and/or breakdown products, via physical or biological processes, which result in structurally similar chemicals (e.g. the metabolic pathway approach of examining related chemicals such as acid/ester/salt). Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach. Therefore, it is reasonable to read-across the information from the acute oral and inhalation studies with H₂SO₄ to address the data gap for the test substance. The rat oral LD₅₀ for H₂SO₄ was 2140 mg/kg, which when corrected for test substance/H₂SO₄ molecular weight differences, would yield an equivalent test substance oral LD₅₀ of 5547 mg/kg. The rat inhalation LC₅₀ for H₂SO₄ was 375 mg/m³,which when corrected for test substance/H₂SO₄ molecular weight differences, would yield an equivalent test substance 4-hour LC₅₀ of 972 mg/m³.

Justification for selection of acute toxicity – oral endpoint
LD50 is based on read across to acute inhalation study with H2SO4 (Scientifically valid study, similar to OECD guideline), which corrected for test substance/H2SO4 molecular weight differences, would yield an equivalent test substance oral LD50 of 5547 mg/kg.

Justification for selection of acute toxicity – inhalation endpoint
LC50 is based on read across to acute inhalation study with H2SO4 (Scientifically valid study, similar to OECD guideline), which corrected for test substance/H2SO4 molecular weight differences, would yield an equivalent test substance 4-hour LC50 of 972 mg/m3

Justification for classification or non-classification

The acute inhalation LC₅₀ in rats with H₂SO₄ was 375 mg/m³, which when corrected for test substance/H₂SO₄ molecular weight differences, would yield an equivalent test substance 4-hour LC₅₀ of 972 mg/m³. Therefore, the test substance is classified as T, R23 (toxic by inhalation (gas, dust/mist) for acute inhalation toxicity according to EU Directive 67/548/EEC and Cat 3 (H331: toxic if inhaled) for acute inhalation toxicity according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) regulation (EC) No. 1272/2008. Since the pH of the substance is ≤2 when in contact with biological fluids at 0.1M or greater, it is classified as a corrosive material. Therefore, the label EUH071(corrosive to the respiratory tract) is required according the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) regulation (EC) No. 1272/2008

Based on the oral LD₅₀ in rats with H₂SO₄ of 2140 mg/kg, which when corrected for test substance/H₂SO₄ molecular weight differences, would yield an equivalent test substance oral LD₅₀ of 5547 mg/kg, no classification is required for acute oral toxicity according to the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Data lacking due to waiving arguments, therefore the test substance cannot be classified for acute dermal toxicity according to the EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.