Dipotassium peroxodisulphate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977-12-21 to 1979-01-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no information on test

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

Disodium persulfate was included in the diet administered to rats for 13 weeks. The effects of three levels of test material were compared by determining body weight, food consumption, blood and urine parameters, the results of ophthalmologic examinations and the findings during gross and microscopic examinations among these groups and a concurrent control group of the same age, sex distribution and derivation.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium peroxodisulphate

EC Number:

231-892-1

EC Name:

Disodium peroxodisulphate

Cas Number:

7775-27-1

Molecular formula:

Na2S2O8

IUPAC Name:

disodium peroxodisulphate

Test animals

Species:

rat

Strain:

other: Charles River CR strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Labs, Inc.; 251 Ballardvale Street; Wilmington, Massachusetts 01887
- Age at study initiation: weanling albino rats
- Weight at study initiation: not indicated
- Fasting period before study: not indicated
- Housing: not indicated
- Diet (e.g. ad libitum): no information available
- Water (e.g. ad libitum): no information available
- Acclimation period: no information available


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not indicated
- Humidity (%): not indicated
- Air changes (per hr): not indicated
- Photoperiod (hrs dark / hrs light): not indicated

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Diet preparation:
The basic feed was Purina laboratory Chow. The diets were prepared in the following manner:
The appropriate amount of sodium persulfate was accurately weighed out on a gram scale and the finely ground with a mortar and pestle. This material was then mixed gradually into 200 grams of Purina Laboratory Chow. This mixture was then placed in a Hobart mixer and the remaining 5,800 grams of Purina Laboratory Chow gradually added to ensure an even mix. The mix time was 30 minutes at completion. Two samples of each diet were taken, placed in labelled bags and returned to the Sponsor for analysis and storage.
Diets were prepared bi-weekly after the Sponsor analyzed the samples of diets prepared at Foster D. Snell and reported that the diets were stable for at least one (1) week. Water and the prepared diet were provided ad libitum for the duration of the study.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

No detailed information on analytical verification available.

Duration of treatment / exposure:

90 days

Frequency of treatment:

No applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
0; 300; 1000; 3000 ppm / 0; 22; 91; 200 mg/kg bw/day.
Basis:
nominal in diet

No. of animals per sex per dose:

20 animals per sex and per dose;

Control animals:

other: yes, plain diet ad libitum

Details on study design:

Initial dosages:
From Day 1 to Day 49, the following dosage concentrations were prepared and fed to the specific treatment groups:
I - 0 ppm (Control);
II - 300 ppm;
III - 1000 ppm;
IV - 3000 ppm
On Day 48, after review of response to that time, the concentration given to the test animals of the Treatment Group III was increased from 1000 to 5000 ppm. The group became group V and received 5000 ppm to the study termination (9 - 13 weeks), thus:
I - 0 (Control);
II - 300 ppm;
III - Ceased at week 8;
IV - 3000
V - 1000/5000

Examinations

Observations and examinations performed and frequency:

Initial body weights of the animals were taken immediately prior to the exposure to the test diets and weekly thereafter. Food consumption data was monitored over a 2-day sampling period each week through week 4 and during weeks 8 and 13 except for group V in which the procedure was repeated during weeks 9, 10, 11 and 12 as well. Compound intake was calculated from food consumption data.
Animals were observed daily for viability and examined weekly during which abnormalities such as signs of masses, abnormal appearance or behaviour were noted.
Clinical parameters:
The following haematological and blood chemical evaluations were carried out on samples drawn from 5 male and 5 female rats of each group during the 13th week of the study.
- Haematologic Examinations: Erythrocyte count; Total and differential leukocyte counts; Haemoglobin; Haematocrit;
- Blood Chemical Examinations: Sodium; Potassium; Calcium; Chloride; Glucose, Blood urea Nitrogen; Creatinine; Bilirubin, Lactic dehydrogenase; Alkaline phosphatase; SGPT; SGOT; Total Protein; Albumin/Globulin ratio;
Individual urine samples were collected from five animals per sex per group initially and during the 5th, 9th and 13th weeks of the study. The following determinations were made: Specific gravity; Glucose; Protein, Ketone bodies; Occult blood; pH;

Sacrifice and pathology:

After 90 days of dosing, subsequent to the previously described clinical examination, all test animals were sacrificed by CO2 asphyxiation and exsanguination. A complete gross examination of the contents of the calvarium and the pleural and peritoneal cavities followed, including determination of the following organ weights: Brain; Liver; Kidney; Adrenals; Spleen, Lungs; Heart, Gonads.
Representative samples of all tissues from each animal were excised, fixed in 10 % buffered formalin, trimmed, embedded in paraffin and stained with haematoxylin and eosin for micropathologic examination. The following tissues from animals of Groups I (Control), IV (3000 ppm) and V (1000/5000 ppm) were examined microscopically: Brain; Pituitary; Salivary Gland; Thyroid; Parathyroids; Heart; Lung; Liver; Spleen; Stomach; Small Intestine; Large Intestine; Pancreas; Kidneys; Urinary Bladder; Adrenals; Gonads; Lymph nodes; Bone; Bone marrow; Muscle; Lesions or masses. After the tissues of the preceding groups were examined microscopically, tissues of the low group (300 ppm) were processed as described for micropathologic examination.

Other examinations:

Ophthalmologic examinations of all animals were carried out initially and during the 13th week of the study.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

effects observed, treatment-related

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Ophthalmological findings:

effects observed, treatment-related

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

All animals survived the study.
Significant differences were seen among the groups in
- Body weights
- Food consumption.
No significant differences were seen among groups in:
- Haematological blood chemical, and urine analytical parameters
- Organ weight and body weight ratios.
Organ weights, organ-to-body weight ratios and type and frequency of grossly observable lesions seen during necropsy were comparable among the four groups.
Intestinal changes were noted among the rats which received 3000 ppm of sodium persulfate for 13 weeks. These changes were seen more frequently among females than males. The former received 50 percent more test material than the latter on a dose per body weight basis. No significant changes were seen among the controls or the groups which received 300 ppm, or 1000 ppm in the diet for eight weeks, followed by 5000 ppm in the diet for the remainder of the study. No other microscopic changes were noted on comparison among these three groups.

Effect levels

1

Dose descriptor:

LOAEL

Effect level:

3 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

2

Dose descriptor:

LOAEL

Effect level:

200 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

3

Dose descriptor:

NOAEL

Effect level:

1 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

4

Dose descriptor:

NOAEL

Effect level:

91 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

LOAEL: 3000 ppm = 200 mg/kg bw/day
NOAEL: 1000 ppm = 91 mg/kg bw/day

Executive summary:

Disodium persulfate was administered in the diet of rats for 13 weeks. Observations included body weight, food consumption, blood and urine parameters. Further ophthalmologic examinations and gross and microscopic examinations were carried out. The concurrent control group was of the same age, sex distribution and derivation. One group of animals received only the basal diet (control group). Others received 300 and 3000 ppm of the test material in the diet. The fourth group received 1000 ppm of the test material in the diet for eight weeks and 5000 ppm of the test material in the diet for the final five weeks (as it was probably suspected that no limit dose with substance related effects would be revealed). All animals survived the study. Significant differences were seen among the groups in body weights and food consumption. No significant differences were seen among groups in Haematological blood chemical, and urine analytical parameters, and organ weight and body weight ratios. Organ weights, organ-to-body weight ratios and type and frequency of grossly observable lesions seen during necropsy were comparable among the four groups. Intestinal changes were noted in rats which received 3000 ppm of sodium persulfate for 13 weeks. These changes were seen more frequently among females than males. The former received 50 percent more test material than the latter on a dose per body weight basis. No significant changes were seen among the controls or the groups which received 300 ppm, or 1000 ppm in the diet for eight weeks, followed by 5000 ppm in the diet for the remainder of the study. No other microscopic changes were noted on comparison among these three groups. LOAEL and NOAEL values of 200 and 91 mg/kg bw /day (3000 and 1000 ppm), respectively were determined.