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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
US-EPA, Fed. Reg. Vol. 43, No. 163 (1978) § 163.81-3
GLP compliance:
Study was performed under the control of a quality assurance unit similar to GLP.
Test type:
traditional method

Test material

Constituent 1
Chemical structure
Reference substance name:
Dihydrogen bis[monoperoxyphthalato(2-)-O1,OO1]magnesate(2-)
EC Number:
EC Name:
Dihydrogen bis[monoperoxyphthalato(2-)-O1,OO1]magnesate(2-)
Cas Number:
Molecular formula:
dihydrogen bis[monoperoxyphthalato(2-)-O1,OO1]magnesate(2-)
Details on test material:
Test material: Magnesium-monoperoxyphthalate-hexahydrate, H48 Bleach
- Source and lot/batch No.of test material: 0525
- Further relevant properties: White powder with a faint pungent odour

Test animals

Details on test animals or test system and environmental conditions:
Source: Charles River (U.K.) Limited
Age/weight at study initiation: 8-10 weeks, 144-160 g (males); 182-212 g (females)
Fasting period before study: 18 h
Diet: ad libitum
Water: ad libitum
Acclimation period: at least 13 d

- Temperature (°C): 21+/-
- Humidity (%): 55+/-20
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
other: Dry, oil-free air
Remark on MMAD/GSD:
EAD (Equivalent Aerodynamic Diameters); median: 1.36 to 2.02 µm
Details on inhalation exposure:
Type or preparation of particles Wright dust feed mechanism (Messrs. L. Adams. Ltd, London, England)
Nominal concentrations:
females: 2.86, 4.23, 5.62, 7.96, 10.81 mg/l air
males: 4.23, 5.62, 7.96, 10.81, 13.31 mg/l air

measured concentrations:
females: 1.15, 1.68, 1.90, 2.47, 3.21 mg/l air
males: 1.68, 1.90, 2.47, 3.21, 3.88 mg/l air
respirable fraction (<5µm EAD)
females: 0.84, 1.20, 1.32, 1.63, 1.94 mg/l air
males : 1.20, 1.32, 1.63, 1.94, 2.17 mg/l air
No. of animals per sex per dose:
5 males/5 females
Control animals:
4 h of sham exposure
Details on study design:
Mortality and clinical signs (frequently during exposure, at least daily thereafter), body weight (daily for the first five days, on Day 8 and weekly thereafter, necropsy of all animals, organ weights from liver, kidneys and lungs, histopathology on lungs, liver, kidneys and any abnormalities.
The acute median lethal concentration and 95% confidence limits were calculated according to the method of Finney (1952), Probit analysis, pp.236-245, C.U.P.

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
1.72 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Seven male and nine female rats died within 36 hours of the start of exposure and further 10 males and 9 females died during the second or third week of observation.
Clinical signs:
other: Clinical signs occurred with dose-relation and were mainly: decreased motor activity, hunched posture, hyperpnoea, bradypnoea, hypopnoea, gasping, cyanosis, piloerection, ungroomed, pigmented orbital secretion, pigmented stain of snout, respiratory rales,
Body weight:
Body weights were continuously reduced in all treated groups.
Gross pathology:
Gross pathology:
a) early decedents (first 3 days): external staining, pulmonary congestion, incomplete collapse, dark, firm appearance of the lung, aerated serous fluid in the trachea
b) late decedents (2nd and 3rd week): external staining and abdominal distension, abnormal gastro-intestinal contents, tympanic appearance of the intestinal tract with occasional cases of congestion or prominence of blood vessels in the wall of the caecum, but only occasional congestion or incomplete collapse of the lung.
c) animals surviving until the end of the study: occasional findings of distension, firm, dark appearance of the abdomen, external staining, sparseness of fur, abnormal gastro-intestinal contents, tympanic appearance of the small intestine, pallor and raised subcapsular areas of the liver, enlargement or prominence of bronchial and cervical lymph nodes, pulmonary changes including incomplete collapse of the lung, pallor and the presence of dark subpleural areas or a subpleural focus.
Other findings:
a) early decedents (first 3 days): perivascular oedema, focal necrosis of the terminal bronchiolar epithelium, proteinaceous exudates within the alveoli, distension of the alveolar ducts and focal accumulation of alveolar macrophages in the lungs, hepatocytic (glycogen) pallor in the liver, slight dilatation of the tubules of the outer cortex and basophilic glomeruli in the kidneys and distension of the lumen of the duodenum, jejunum and ileum.
b) late decedents (2nd and 3rd week): perivascular oedema of the lungs, reduction in the incidence of hepatocytic (glycogen) pallor in the liver.
c) animals surviving until the end of the study: slight treatment-related increase in granulomatous pneumonia and slight reduction of hepatocytic (glycogen) pallor.

Organ weights:
Organ weight analysis of lungs, liver and kidneys did not reveal treatment-related differences except for a marked increase of lung weights of animals that died within 36 hours of exposure.

Any other information on results incl. tables

LC50       Males: 1.97 mg/L; females: 1.57 mg/L; Combined sexes: 1.72 mg/L of air (28 days, calculated by probit analysis)

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
The acute median lethal concentration for H48 bleach (LC50, 4 hours) was 1.72 mg/L of air for the combined sex (1.97 mg/L for males, 1.57 mg/L for females).
Executive summary:

The acute inhalation toxicity (LC50) of H 48 bleach, was investigated in groups of 5 male and 5 female Wistar rats after 4 h of nose-only exposure at concentrations of 1.15 –3.88 mg/L air.

A 4 h nose-only exposure of the animals to H48 bleach (Magnesium-monoperoxyphthalate-hexahydrate) aerosol produced significant toxic effects which were characterised by either rapid death due to acute respiratory insufficiency or delayed death associated with progressive debility which was not directly attributable to the degree of pulmonary changes observed. Early stages of intoxications revealed acute morphological changes of the lungs connected with lung weight increase in decedents, whereas later stages of findings in decedents or animals sacrificed at termination after 28 days were associated with lesions confined to the gastro-intestinal tract. It can be assumed that the acute effects are directly related to lung damage in the animals (massive pulmonary oedema) whereas the delayed occurrence of toxic effects is a result of systemic effects of degradation products. The gastrointestinal lesions may be attributed to the formation of H2O2 and its swallowing as a result from tracheal regurgitation.

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