Registration Dossier

Administrative data

Description of key information

Disodium persulfate was tested for repeated dose oral toxicity in rats in a 90-day subchronic study. LOAEL and NOAEL values of 200 mg/kg bw/day and 91 mg/kg bw/day were determined, respectively. In addition Persulfate Category data was available. Read-across data included a NOAEL of 131.5 mg/kg bw/day for subacute oral toxicity and a NOAEC of 10.3 mg/m³ for subchronic inhalation toxicity for dipotassium persulfate and diammonium persulfate, respectively. Repeated dose toxicity via the dermal route was waived, but a NOEAL calculated for chemical risk assessment resulting in a dermal NOAEL of 91 mg/kg bw/day assuming 100 % absorption through the skin.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
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 proof for guideline (OECD, EPA OPP, or other); no information on test animal treatment parameters.
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
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
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
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
0 ppm nominal in diet
Dose / conc.:
22 mg/kg bw/day (nominal)
Remarks:
300 ppm nominal in diet
Dose / conc.:
91 mg/kg bw/day (nominal)
Remarks:
1000 pm nominal in diet
Dose / conc.:
200 mg/kg bw/day (nominal)
Remarks:
3000 ppm nominal in diet
No. of animals per sex per dose:
20 animals per sex and per dose
Control animals:
yes, plain diet
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
Positive control:
The animals in the positive control were fed the plain diet ad libitum.
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.
- Hematologic 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.
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. This suggests that the effect was a function of both levels of test material and time of administration.
No other microscopic changes were noted on comparison among these three groups.
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
Key result
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
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
Key result
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
Key result
Critical effects observed:
not specified
Conclusions:
LOAEL: 200 mg/kg bw/day = 3000 ppm
NOAEL: 91 mg/kg bw/day = 1000 ppm
Executive summary:

Disodium persulfate was included in the diet of 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 between a concurrent control group 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 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. This suggests that the effect was a function of both levels of test material and time of administration. No other microscopic changes were noted on comparison among these three groups. A LOAEL and NOAEL values of 200 and 91 mg/kg bw /day (3000 and 1000 ppm), respectively were determined.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
91 mg/kg bw/day
Study duration:
subchronic
Species:
rat
System:
gastrointestinal tract
Organ:
duodenum

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEC
Effect level:
10.3 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
clinical signs
food consumption and compound intake
gross pathology
haematology
histopathology: non-neoplastic
mortality
ophthalmological examination
organ weights and organ / body weight ratios
urinalysis
Key result
Dose descriptor:
NOEC
Effect level:
5 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
clinical signs
food consumption and compound intake
gross pathology
haematology
histopathology: non-neoplastic
mortality
ophthalmological examination
organ weights and organ / body weight ratios
urinalysis
Key result
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
10.3 mg/m³
Study duration:
subchronic
Experimental exposure time per week (hours/week):
6
Species:
rat

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEC
Effect level:
10.3 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
clinical signs
food consumption and compound intake
gross pathology
haematology
histopathology: non-neoplastic
mortality
ophthalmological examination
organ weights and organ / body weight ratios
urinalysis
Key result
Dose descriptor:
NOEC
Effect level:
5 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
clinical signs
food consumption and compound intake
gross pathology
haematology
histopathology: non-neoplastic
mortality
ophthalmological examination
organ weights and organ / body weight ratios
urinalysis
Key result
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
10.3 mg/m³
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Disodium persulfate was tested for repeated dose toxicity in rats in a 90-day study. All animals survived during the study. LOAEL and NOAEL values of 200 mg/kg bw/day (3000 ppm) and 91 mg/kg bw/day (1000 ppm) respectively, were determined. Intestinal changes (examined microscopically) were noted among the rats which received 3000 ppm of sodium persulfate for 13 weeks, considered local primary effects while significant differences in body weight and food consumption in this dose group were considered secondary systemic effects. In addition read-across data for substances of the Persulfate Category was available. All substances of the Persulfate Category share the same anionic persulfate moiety and similar toxicological properties. Repeated dose toxicity data was available for diammonium persulfate and dipotassium persulfate. Of the Persulfate Category, dipotassium persulfate and diammonium persulfate were tested for subacute oral repeated dose toxicity, resulting in NOAEL values of 131.5 mg/kg bw/day and 41.1 mg/kg bw/day. The apparent difference in subacute toxicity of persulfates was considered to be due to the ammonium cation and its effects. Diammonium persulfate, when dissociated in solution, exists as simple alkali metal cation and persulfate anion, with the ammonium cation in equilibrium with ammonia depending on the solution’s pH. Dissolution of ammonium persulfate itself will also affect pH. This may complicate the toxicological profile of ammonium persulfate (EC JRC IHCP Report, 2007). Disodium persulfate was tested in a subchronic 90-day inhalation toxicity study. A NOAEC value of 10.3 mg/m³ was determined.

Worst-case values considered for safety assessment were:

Repeated dose oral (NOAEL): 91 mg/kg bw/day

Repeated dose inhalation (NOAEC): 10.3 mg/m³

Justification for classification or non-classification

Based on the results obtained, substances of the Persulfate Category were not classified and labelled for repeated dose toxicity according Regulation 1272/2008/EC (CLP), as amended for the fifteenth time in Regulation (EU) 2020/1182.