Diammonium peroxodisulphate

Endpoint summary

Description of key information

The oral repeated dose toxicity of diammonium persulfate was based on a subacute oral toxicity study and a read across approach from dipotassium persulfate and disodium persulfate, as these substances show similar toxicological properties. A subacute NOAEL of 41.1 mg/kg bw/day and a subchronic NOAEL of 91 mg/kg bw/day were determined. Diammonium persulfate was tested for subchronic inhalation toxicity. A NOAEC value of 10.3 mg/m³ was determined. Repeated dose toxicity via the dermal route was waived for the Persulfate Category.

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:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

READ ACROSS CATEGORY APPROACH
A category group was formed with dipotassium peroxodisulphate (KPS), disodium peroxodisulphate (SPS) and diammonium peroxodisulphate (APS). Several physico-chemical, fate, ecotoxicological and toxicological endpoints were assessed using the category approach. Please refer to the read across justification in chapter 13 for further information.

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Effect level:

91 mg/kg bw/day (nominal)

Based on:

other: SPS

Sex:

male/female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

Key result

Critical effects observed:

no

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

91 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Qualifier:

according to guideline

Guideline:

EPA OPP 82-4 (90-Day Inhalation Toxicity)

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River laboratories Inc.; Portage, MI
- Age at study initiation: 39 days
- Weight at study initiation: no information available
- Fasting period before study: no information available
- Housing: individually in suspended, stainless steel wire-mesh cages
- Diet: certified Rodent Lab Die (PMI Nutrition International, Inc.; ad libitum
- Water: tap water ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 40 - 60 % R.H.
- Air changes: no information available
- Photoperiod: 12 hrs dark/12 hrs light

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: Average mass median aerodynamic diameters (MMAD) and geometric standard deviation (GSD) for the exposure levels:
5 mg/m³: 2.5 +/- 1.85 µm;
10 mg/m³: 2.7 +/- 1.83 µm;
25 mg/m³: 2.5 +/- 1.80 µm.

Details on inhalation exposure:

Animals were exposed simultaneously in four 2.0 m³ stainless steel and glass whole-body inhalation exposure chambers (Hazelton 2000 type). One chamber was dedicated for each group for the duration of the study. Twenty animals per sex per exposure group were individually caged in two cage batteries that were rotated daily through various cage positions in the chamber.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Actual exposure concentrations were measured using standard gravimetric methods. Four samples per day were collected from each exposure group during the first month of exposure and two samples per day thereafter. Samples were collected on 25-mm glass-fiber filters (type A/E, Gelman Sciences, Ann Arbor, MI) held in open-face filter holders. Aerosol particle size was determined once for each exposure group during each week. The results were expressed in terms of the mass median aerodynamic diameter (MMAD) and the geometric standard deviation.

Duration of treatment / exposure:

Diammonium persulfate was administered 6 h/day, 5 days/week, for 13 consecutive weeks

Frequency of treatment:

6 h/day

Dose / conc.:

0 mg/m³ air (analytical)

Dose / conc.:

5 mg/m³ air (analytical)

Dose / conc.:

10.3 mg/m³ air (analytical)

Dose / conc.:

25 mg/m³ air (analytical)

No. of animals per sex per dose:

20 animals per sex per exposure group.

Control animals:

yes, concurrent no treatment

Details on study design:

- Animals were exposed simultaneously in four 2.0 m³ stainless steel and glass whole-body inhalation exposure chambers (Hazelton 2000 type). One chamber was dedicated for each group for the duration of the study. Twenty animals per sex per exposure group were individually caged in two cage batteries that were rotated daily through various cage positions in the chamber. Ammonium persulfate was administered 6 h/day, 5 days/week, for 13 consecutive weeks to target exposure levels of 5, 10, and 25 mg/m³. The exposure levels were based on a no-effect level of 10 mg/m³ from a 4-week range finding study using 3.3, 10.3 and 32.5 mg/m³ of diammonium persulfate.
- An identical group of animals was exposed to clean filtered air and served as control group.

Positive control:

Not indicated.

Observations and examinations performed and frequency:

Animals were observed twice daily for viability. Individual physical observations were conducted weekly, beginning 1 wk prior to initiation of exposure. In addition, animals were observed within the chamber at the midpoint of each exposure and again when the animals were removed from the chamber. During the recovery period, clinical examinations were performed once daily.

Sacrifice and pathology:

After completion of 13 weeks of exposure, 10 animals per sex per group were randomly selected, euthanized and necropsied. Of the remaining animals, 5 animals per sex per dose group were maintained from either 4- or 13-week postexposure recovery periods and then euthanized and necropsied.

Statistics:

All analyses were conducted using two-tailed tests for minimum significance levels of 1 % and 5 %, comparing the treatment groups to the control group by sex. All statistics were performed by a Digital MicroVAX 3400 computer. Body weight, body weight change, food consumption clinical pathology and absolute and relative organ weight data were subjected to a one-way variance (ANOVA) followed by Dunnett's test (Dunnett, 1964) when appropriate.

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, non-treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

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

Details on results:

There were no exposure-related deaths during the study. Increased respiration rates were noted in both males and females in the 25 mg/m³ group, and in a few animals in the 10.3 mg/m³ group. The incidence of these clinical signs decreased to zero during the first weeks of the recovery period. Body weights for both males and females in the 25 mg/m³ group were significantly depressed during most of the exposure period compared to the control group. By the end of the recovery period, body weights for the exposed animals were similar to the control group values. Lung weights were elevated in the 25 mg/m³ group after 13 wk of exposure, but were similar to controls at 6 wk postexposure. Irritation of the trachea and bronchi/bronchioles was noted microscopically after 13 weeks of exposure to 25 mg/m³. These lesions had recovered by 6 wk postexposure.
Based on these results, the no-observed-adverse-effect concentration (NOAEC) was 10.3 mg/m³, while the no-observed-effect concentration (NOEC) for exposure of rats to a dust aerosol of ammonium persulfate was 5.0 mg/m³.

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 signs

food consumption and compound intake

histopathology: non-neoplastic

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 signs

food consumption and compound intake

histopathology: non-neoplastic

Critical effects observed:

not specified

Conclusions:

The no-observed-adverse effect level (NOAEC) was 10.3 mg/m³, while the no-observed-effect level (NOEC) for exposure of rats to a dust aerosol of diammonium persulfate was 5.0 mg/m³. Furthermore, indications for respiratory tract irritation was observed in animals administered with 25 mg/m³ of diammonium persulfate.

Executive summary:

The subchronic inhalation toxicity of ammonium persulfate was characterized using Sprague-Dawley rats (20/sex/group) at respirable dust concentrations of 0, 5.0, 10.3, and 25 mg/m³. Whole-body exposures were conducted 6 h/day, 5 days/week for 13 weeks. Gravimetric airborne test material samples were taken daily and particle size samples were taken weekly from each exposure chamber for analysis. Ten animals/sex/group were necropsied after 13 wk of exposure, and 5 animals/sex/group were held for 6- and 13-wk recovery periods. Animals were observed for clinical signs. Effects on body weight, food consumption clinical chemistry and haematology, ophthalmologic parameters organ weights, gross lesions, and histopathology were evaluated. There were no exposure-related deaths during the study. Increased respiration rates were noted in both males and females  in the 25 mg/m³ group, and in a few animals in the 10.3 mg/m³ group. The incidence of these clinical signs decreased to zero during the first weeks of the recovery period. Body weights for both males and females in the 25 mg/m³ group were significantly depressed during most of the exposure period compared to the control group. By the end of the recovery period, body weights for the exposed animals were similar to the control group values. Lung weights were elevated in the 25 mg/m³ group after 13 wk of exposure, but were similar to controls at 6 wk postexposure. Irritation of the trachea and bronchi/bronchioles was noted microscopically after 13 weeks of exposure to 25 mg/m³. These lesions had recovered by 6 wk postexposure.

Based on these results, the no-observed-adverse-effect concentration (NOAEC) was 10.3 mg/m³, while the no-observed-effect concentration (NOEC) for exposure of rats to a dust aerosol of ammonium persulfate was 5.0 mg/m³.

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):

30

Species:

rat

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Qualifier:

according to guideline

Guideline:

EPA OPP 82-4 (90-Day Inhalation Toxicity)

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River laboratories Inc.; Portage, MI
- Age at study initiation: 39 days
- Weight at study initiation: no information available
- Fasting period before study: no information available
- Housing: individually in suspended, stainless steel wire-mesh cages
- Diet: certified Rodent Lab Die (PMI Nutrition International, Inc.; ad libitum
- Water: tap water ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 40 - 60 % R.H.
- Air changes: no information available
- Photoperiod: 12 hrs dark/12 hrs light

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: Average mass median aerodynamic diameters (MMAD) and geometric standard deviation (GSD) for the exposure levels:
5 mg/m³: 2.5 +/- 1.85 µm;
10 mg/m³: 2.7 +/- 1.83 µm;
25 mg/m³: 2.5 +/- 1.80 µm.

Details on inhalation exposure:

Animals were exposed simultaneously in four 2.0 m³ stainless steel and glass whole-body inhalation exposure chambers (Hazelton 2000 type). One chamber was dedicated for each group for the duration of the study. Twenty animals per sex per exposure group were individually caged in two cage batteries that were rotated daily through various cage positions in the chamber.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Actual exposure concentrations were measured using standard gravimetric methods. Four samples per day were collected from each exposure group during the first month of exposure and two samples per day thereafter. Samples were collected on 25-mm glass-fiber filters (type A/E, Gelman Sciences, Ann Arbor, MI) held in open-face filter holders. Aerosol particle size was determined once for each exposure group during each week. The results were expressed in terms of the mass median aerodynamic diameter (MMAD) and the geometric standard deviation.

Duration of treatment / exposure:

Diammonium persulfate was administered 6 h/day, 5 days/week, for 13 consecutive weeks

Frequency of treatment:

6 h/day

Dose / conc.:

0 mg/m³ air (analytical)

Dose / conc.:

5 mg/m³ air (analytical)

Dose / conc.:

10.3 mg/m³ air (analytical)

Dose / conc.:

25 mg/m³ air (analytical)

No. of animals per sex per dose:

20 animals per sex per exposure group.

Control animals:

yes, concurrent no treatment

Details on study design:

- Animals were exposed simultaneously in four 2.0 m³ stainless steel and glass whole-body inhalation exposure chambers (Hazelton 2000 type). One chamber was dedicated for each group for the duration of the study. Twenty animals per sex per exposure group were individually caged in two cage batteries that were rotated daily through various cage positions in the chamber. Ammonium persulfate was administered 6 h/day, 5 days/week, for 13 consecutive weeks to target exposure levels of 5, 10, and 25 mg/m³. The exposure levels were based on a no-effect level of 10 mg/m³ from a 4-week range finding study using 3.3, 10.3 and 32.5 mg/m³ of diammonium persulfate.
- An identical group of animals was exposed to clean filtered air and served as control group.

Positive control:

Not indicated.

Observations and examinations performed and frequency:

Animals were observed twice daily for viability. Individual physical observations were conducted weekly, beginning 1 wk prior to initiation of exposure. In addition, animals were observed within the chamber at the midpoint of each exposure and again when the animals were removed from the chamber. During the recovery period, clinical examinations were performed once daily.

Sacrifice and pathology:

After completion of 13 weeks of exposure, 10 animals per sex per group were randomly selected, euthanized and necropsied. Of the remaining animals, 5 animals per sex per dose group were maintained from either 4- or 13-week postexposure recovery periods and then euthanized and necropsied.

Statistics:

All analyses were conducted using two-tailed tests for minimum significance levels of 1 % and 5 %, comparing the treatment groups to the control group by sex. All statistics were performed by a Digital MicroVAX 3400 computer. Body weight, body weight change, food consumption clinical pathology and absolute and relative organ weight data were subjected to a one-way variance (ANOVA) followed by Dunnett's test (Dunnett, 1964) when appropriate.

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, non-treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

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

Details on results:

There were no exposure-related deaths during the study. Increased respiration rates were noted in both males and females in the 25 mg/m³ group, and in a few animals in the 10.3 mg/m³ group. The incidence of these clinical signs decreased to zero during the first weeks of the recovery period. Body weights for both males and females in the 25 mg/m³ group were significantly depressed during most of the exposure period compared to the control group. By the end of the recovery period, body weights for the exposed animals were similar to the control group values. Lung weights were elevated in the 25 mg/m³ group after 13 wk of exposure, but were similar to controls at 6 wk postexposure. Irritation of the trachea and bronchi/bronchioles was noted microscopically after 13 weeks of exposure to 25 mg/m³. These lesions had recovered by 6 wk postexposure.
Based on these results, the no-observed-adverse-effect concentration (NOAEC) was 10.3 mg/m³, while the no-observed-effect concentration (NOEC) for exposure of rats to a dust aerosol of ammonium persulfate was 5.0 mg/m³.

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 signs

food consumption and compound intake

histopathology: non-neoplastic

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 signs

food consumption and compound intake

histopathology: non-neoplastic

Critical effects observed:

not specified

Conclusions:

The no-observed-adverse effect level (NOAEC) was 10.3 mg/m³, while the no-observed-effect level (NOEC) for exposure of rats to a dust aerosol of diammonium persulfate was 5.0 mg/m³. Furthermore, indications for respiratory tract irritation was observed in animals administered with 25 mg/m³ of diammonium persulfate.

Executive summary:

The subchronic inhalation toxicity of ammonium persulfate was characterized using Sprague-Dawley rats (20/sex/group) at respirable dust concentrations of 0, 5.0, 10.3, and 25 mg/m³. Whole-body exposures were conducted 6 h/day, 5 days/week for 13 weeks. Gravimetric airborne test material samples were taken daily and particle size samples were taken weekly from each exposure chamber for analysis. Ten animals/sex/group were necropsied after 13 wk of exposure, and 5 animals/sex/group were held for 6- and 13-wk recovery periods. Animals were observed for clinical signs. Effects on body weight, food consumption clinical chemistry and haematology, ophthalmologic parameters organ weights, gross lesions, and histopathology were evaluated. There were no exposure-related deaths during the study. Increased respiration rates were noted in both males and females  in the 25 mg/m³ group, and in a few animals in the 10.3 mg/m³ group. The incidence of these clinical signs decreased to zero during the first weeks of the recovery period. Body weights for both males and females in the 25 mg/m³ group were significantly depressed during most of the exposure period compared to the control group. By the end of the recovery period, body weights for the exposed animals were similar to the control group values. Lung weights were elevated in the 25 mg/m³ group after 13 wk of exposure, but were similar to controls at 6 wk postexposure. Irritation of the trachea and bronchi/bronchioles was noted microscopically after 13 weeks of exposure to 25 mg/m³. These lesions had recovered by 6 wk postexposure.

Based on these results, the no-observed-adverse-effect concentration (NOAEC) was 10.3 mg/m³, while the no-observed-effect concentration (NOEC) for exposure of rats to a dust aerosol of ammonium persulfate was 5.0 mg/m³.

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

Of the Persulfate Category, diammonium persulfate, dipotassium persulfate and disodium persulfate were tested for oral repeated dose toxicity. Diammonium persulfate was tested for subacute oral toxicity in rats in a 28-day study. A NOAEL of 41.1 mg/kg bw/day was determined. Dipotassium persulfate was tested for subacute oral toxicity in rats in a 28-day study. A NOAEL value of 131.5 mg/kg bw/day was determined. 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 for repeated dose toxicity in rats in a 90-day study. Intestinal changes (examined microscopically) were noted among the rats of the highest dosing group (200 mg/kg bw/d), and are considered local primary effects while significant differences in body weight and food consumption in this dose group were considered secondary systemic effects. A local NOAEL of 91 mg/kg bw/day was determined. Of the Persulfate Category diammonium persulfate was tested for subchronic inhalation toxicity. A local NOAEC value of 10.3 mg/m³/day was determined. A read across approach was applied for dipotassium persulfate and disodium persulfate using results obtained with diammonium persulfate, as the substances were considered to exhibit similar toxicological properties. A repeated dose dermal toxicity study was waived for the Persulfate Category as the physicochemical properties suggest no evidence of significant absorption by the dermal route in accordance with column 2 REACH Regulation No. 1907/2008 Annex VIII, section 8.6.2.

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/day

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 to Regulation 1272/2008/EC (CLP), as amended for the fifteenth time in Regulation (EU) 2020/1182.