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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:
key study
Study period:
2001-01-04 - 2001-09-03
Reliability:
1 (reliable without restriction)
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.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
March 1996
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
September 1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Pentapotassium bis(peroxymonosulphate) bis(sulphate)
EC Number:
274-778-7
EC Name:
Pentapotassium bis(peroxymonosulphate) bis(sulphate)
Cas Number:
70693-62-8
Molecular formula:
H3K5O18S4
IUPAC Name:
pentapotassium bis(peroxymonosulphate) bis(sulphate)
Details on test material:
- Name of test material (as cited in study report): Oxone® Monopersulfate Compound
- Description: White powder
- Analytical purity: 95.7 % KMPS triple salt
- Lot No.: H-24607

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan U. K. Ltd., Bicester, Oxon, UK
- Age at study initiation: 5 - 7 weeks
- Weight at study initiation: 108 g (males); 88.5 g (females)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 % w/v and 20 % w/v (corresponding to 20 mg/mL and 200 mg/mL, respectively)
- Total volume applied: 10 mL/kg bw
Doses:
200 mg/kg bw (3 males; 3 females) + 2000 mg/kg bw (3 females)

No. of animals per sex per dose:
3 rats per sex and group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Examinations:
* clinical observations: at frequent intervals during test day 1, twice daily during days 2 – 15; all abnormalities were recorded
* mortality/viability: at least twice daily
* body weight: on test day 1 (prior to administration), 8 and 15
* necropsy (day 15): macroscopical examination of all animals (survivors and decedents) which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.
Statistics:
Toxicity was estimated without use of a statistical model.
Further more, when applying OECD 423 (Acute Toxic Class Method) for the determination of the acute oral LD50, a statistical method is not considered to be required, as this particular method does not yield the determination of an accurate LD50 figure but apart from specific situations gives rather an estimate on the range of the LD50.

Results and discussion

Preliminary study:
not indicated
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Mortality:
Since no deaths occurred at a dose level of 200 mg/kg bw and all animals died after the administration of 2000 mg/kg bw the LD50 (oral) was determined to be 500 mg/kg bw according to OECD 423 Annex 2c.
Clinical signs:
- Both dosages/all rats: piloerection, first noted approximately one hour after dosing
- 200 mg/kg bw: no further signs of toxicity observed
- 2000 mg/kg bw: all females showed hunched posture, lethargy, abnormal gait, reduced body temperature, body tremors, shallow respiration and pallor of skin with dull eyes in two females and partially closed eyelids and red staining around the uro/genital area in one female.
Body weight:
Body weight loss was recorded for two of three females treated with 2000 mg/kg bw .
Gross pathology:
- All females treated with 2000 mg/kg bw died (two animals were found dead 6 h after administration, one on day 2). The animals revealed congestion in the subcutaneous tissue, brain, heart, lungs and spleen with pallor of the kidneys and pale patches on the liver and red fluid contents of the urinary bladder in one or more animals. Congestion and fluid contents were noted in the stomach and along the alimentary tract and in the urinary tract with enlarged, swollen or thickened tissues and dark and pale discolouration of the lining also seen in the stomach for all animals.
- No abnormalities were revealed for surviving animals.
Other findings:
not indicated

Any other information on results incl. tables

Table 1: Mortality data

Dose
(mg/kg bw)

No. of deaths in group of 3

Day*

-

-

1
6 hours

2
a
             b

3 to 14
a
             b

200

0/3 Male
0/3 Female

0
0

0             0
0
             0

0             0
0
             0

2000

3/3 Female

2

1             -

-             -

*     The day/time indicated is the time that the animal was observed to die or found dead.

a    First observation
b
    Second observation
-
    Not applicable

Table 2: Signs of reaction to treatment

Clinical signs

No. of rats in groups of 3 showing signs
Dose (mg/kg)

200

2000

Male

Female

Female

Piloerection

3

3

3

Hunched posture

0

0

3

Lethargy

0

0

3

Abnormal gait

0

0

3

Reduced body temperature

0

0

3

Body tremors

0

0

3

Shallow respiration

0

0

3

Pallor of the skin

0

0

3

Dull eyes

0

0

2

Partially closed eyelids

0

0

1

Red staining around the uro/genital area

0

0

1

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability). Since no deaths occurred at a dose level of 200 mg/kg bw and all animals died after the administration of 2000 mg/kg bw the LD50 (oral) was determined to be 500 mg/kg bw according to OECD 423 Annex 2c. Based on Directive 67/548/EC (DSD) and Regulation 1272/2008/EC (CLP), KMPS triple salt is classified as harmful if swallowed (cat. 4 (H302), Xn, R22).
Executive summary:

Materials and methods

Six (three male and three female) Sprague Dawley (CD) rats received a single dose of 200 mg KMPS triple salt/kg bw and another group of three females received 2000 mg KMPS triple salt/kg bw. The substance was administered by gavage at a constant volume of 10 mL/kg bw in distilled water as the vehicle. Animals were fastened over night prior to administration of the test material. Post-observation period was 14 days. A regular examination on clinical signs of toxicity and mortality/viability was performed. Body weights were determined pre-treatment on day 1, on days 8 and 15, or at death. All animals were subjected to a macroscopic examination on day 15.

Results and discussion

Please refer to tables 1 and 2, which are presented under "Remarks on results including tables and figures".

Following a single oral administration of KMPS triple salt by gavage to male and female Sprague Dawley (CD) rats at dose levels of 200 + 2000 mg/kg bw, all three females dosed with 2000 mg/kg bw died (two approximately 6 hours after dosing and one within 22 hours of dosing). A body weight loss was recorded for two of the decedents. Clinical signs at the 2000 mg/kg bw dosage were characterised by hunched posture, lethargy, abnormal gait, reduced body temperature, body tremors, shallow respiration and pallor of skin with dull eyes in two females and partially closed eyelids and red staining around the uro/genital area in one female. The animals revealed congestion in the subcutaneous tissue, brain, heart, lungs and spleen with pallor of the kidneys and pale patches on the liver and red fluid contents of the urinary bladder in one or more animals. Congestion and fluid contents were noted in the stomach and along the alimentary tract and in the urinary tract with enlarged, swollen or thickened tissues and dark and pale discolouration of the lining also seen in the stomach for all animals. No signs of toxicity (except of piloerection) observed were observed in animals of the 200 mg/kg bw dose group.

Recovery of surviving rats, as judged by external appearance and behaviour, was complete by day 3. No abnormalities were revealed for surviving animals.