Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2001
Reliability:
1 (reliable without restriction)
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: The study was conducted in compliance with the U.S. Environmental Protection Agency (EPA) and Organization for Economic Cooperation and development (OECD) Good Laboratory Practices (U.S. EPA, 1989; OECD, 1992).
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: ammonium persulfate
- Molecular formula: (NH4)2 S2 O8
- Molecular weight: 228.2
- Substance type: inorganic
- Physical state: solid
- Purity test date: no information available
- Lot/batch No.: no information available
- Expiration date of the lot/batch: no information available
- Stability under test conditions: stable
- Storage condition of test material: at room temperature, in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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

Administration / exposure

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-fibre 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
Doses / concentrations
Remarks:
Doses / Concentrations:
0; 5; 10.3; 25 mg/m³
Basis:
analytical conc.
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:
NA

Examinations

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 post-exposure 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.

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:
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 post exposure. 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 post exposure.
Based on these results, the no-observed-adverse-effect level (NOAEL) was 10.3 mg/m³, while the no-observed-effect level (NOEL) for exposure of rats to a dust aerosol of ammonium persulfate was 5.0 mg/m³.

Effect levels

open allclose all
Dose descriptor:
NOAEC
Effect level:
10.3 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
ophthalmological examination
haematology
clinical biochemistry
urinalysis
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
Dose descriptor:
NOEC
Effect level:
5 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
ophthalmological examination
haematology
clinical biochemistry
urinalysis
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

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 diammonium persulfate was examined in 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. Based on these results, 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. Diammonium persulfate revealed in the study respiratory tract irritation properties as 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 post exposure.