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Description of key information

The acute oral toxicity of H 48 bleach was 2262 mg/kg bw. in the combined sex (2201 mg/kg in males, 2357 mg/kg in females).

According to CLP GHS, H 48 bleach requires no classification, as the acute oral LD50 was >2000 mg/kg of body weight.

The acute dermal toxicity of H 48 bleach was >2000 mg/kg bw. in the combined sex. The LD50 is > 2000 mg/kg bw.

In an acute inhalationstudy 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).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
OECD 401 (1987)
Deviations:
not applicable
GLP compliance:
no
Remarks:
Study was performed under the control of a quality assurance unit similar to GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
CD-1
Sex:
male/female
Details on test animals or test system and environmental conditions:
Source Charles River (U.K). Limited, Margate, Kent
Age/weight at study initiation 108-152 g (males); 100-155 g (females), both about 6 weeks old
Acclimation period: 6 wk
Fasting period before study: 18 h


Temperature 22 ± 2°C
Relative humidity 50 - 70% R.H.



Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Concentration in vehicle: No data
Total volume applied: H 48 bleach: Not exceeding 80 mL/kg bw; Detergent base: 20 mL/kg bw; 10 % H 48 bleach in detergent base: 20 mL/kg bw
Doses:
Dose/Concentration: H 48 bleach: 1200, 1427, 1697, 2018, 2400, or 2854 mg /kg bw; Detergent base: 5000 mg /kg bw; 10 % H 48 bleach in detergent base: 5000 mg /kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
Clinical examinations: three times (during the first hour p.a. and twice daily thereafter. Body weights on days 1, 8 and at termination. Necropsy from all pre-terminal deaths and all survivors at termination.

Statistics:
Method of determination of LD50: Probit analysis; Finney (1952), pp 236-245; Cambridge University Press or moving average interpolation according to Thompson (1947), Bact. Rev.11, 115 and Biometrics 8, 51 (in case the Probit analysis failed to demonstrate a linear dosage/mortality response)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 262 mg/kg bw
Based on:
test mat.
Mortality:
Death occurred after dosages of 1427 mg/kg and above (for further details see Table 1-1).
Clinical signs:
Principal signs at all dosages were decreased motor activity and hunched posture. Less frequent signs were proneness, ataxia, muscle spasticity, piloerection and signs of respiratory distress.
Body weight:
Surviving animals had expected weight gains during the 14-day observation period.
Gross pathology:
External: Muzzle stained; perianal staining;
Internal: Abnormal gastro-intestinal contents (fluid, mucus, creamy material) and congestion of the pyloric wall.
Occasional findings were: Cases of brain congestion, mottled appearance of the liver, incomplete collapse and pale-green areas on all lung lobes.

LD50 2201 mg/kg in males and 2357 mg/kg in females

Dose

Number of dead /
number of investigated

Time of death (range)

Observations

H 48 bleach

M(ales)

F(emales)

 

 

1200 mg/kg

0/5

0/5

-

Day 1, F: Decreased motor activity (5/5), hunched (2/5)

1427 mg/kg

0/5

1/5

Day 1, 4h after dosing

Day 1, M: Decreased motor activity (5/5), hunched (5/5)
Day 1, F: Decreased motor activity (5/5), hunched (5/5)

1697 mg/kg

0/5

0/5

 

Day 1, M: Decreased motor activity (5/5), hunched (5/5)
Day 1, F: Decreased motor activity (5/5), hunched (5/5)

2018 mg/kg

3/5

2/5

Day 1, 2-4 h after dosing

Day 1, M: Decreased motor activity (5/5), hunched (5/5)
ataxia (4/5), muscular spastic (3/5), prone (3/5)

Day 1, F: Decreased motor activity (5/5), hunched (5/5)
ataxia (3/5) prone (3/5)

2400 mg/kg

2/5

2/5

Day 1, 4 h after dosing – Day 2, a.m.

Day 1, M: Decreased motor activity (5/5), hunched (5/5)
ataxia (2/5), muscular tremor (2/5)

Day 1, F: Decreased motor activity (5/5), hunched (5/5)
ataxia (2/5) prone (2/5), muscular tremor (2/5)

2854 mg/kg

5/5

4/5

Day 1, 1 h after dosing – Day 2, a.m

Day 1, M: Lethargic (2/5), decreased motor activity (5/5), hunched (5/5), bradypnoea (3/5), hyperpnoea (5/5), piloerection (5/5)

Day 1, F: Lethargic (2/5), decreased motor activity (5/5), prone (1/5), hunched (5/5), ataxia (3/5), bradypnoea (3/5), hyperpnoea (5/5), gasping (1/5), piloerection (2/5)

LD50value

Males: 2201 mg/kg; Females: 2357 mg/kg; Combined sexes: 2262 mg/kg (Probit analysis) (Thompson’s moving average interpolation for males))

 

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute oral toxicity of H 48 bleach was 2262 mg/kg bw. in the combined sex (2201 mg/kg in males, 2357 mg/kg in females).
According to Directive 67/548/EEC and CLP GHS, H 48 bleach requires no classification, as the acute oral LD50 was >2000 mg/kg of body weight.
Executive summary:

The acute oral toxicity of H 48 bleach was investigated in groups of 5 fasted male and female Charles River CD rats after a single oral administration. Dosages for H 48 bleach ranged from 1200 to 2854 mg/kg bw. Animals treated with H 48 displayed signs of reaction to treatment at all dose levels (principal signs: decreased motor activity and hunching). Deaths occurred at doses of 1427 mg/kg and above on Day 1 or during the first overnight period. Necropsy of decedents of animals dosed with H 48 bleach revealed externally muzzle and, occasionally perianal staining. Internal findings included abnormal gastro-intestinal contents, pallor of the pyloric walls and, occasionally, brain congestion and mottled appearance of the liver.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 262 mg/kg bw
Quality of whole database:
Study was performed under the control of a quality assurance unit similar to GLP

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
US-EPA, Fed. Reg. Vol. 43, No. 163 (1978) § 163.81-3
GLP compliance:
no
Remarks:
Study was performed under the control of a quality assurance unit similar to GLP.
Test type:
traditional method
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
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

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-
- Humidity (%): 55+/-20
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
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)
Concentrations:
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:
total
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:
yes
Remarks:
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.
Statistics:
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.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1.72 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
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:
Histopathology:
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.

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)

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1 720 mg/m³
Quality of whole database:
Guideline study

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Method described in 16 CFR Part1500.3 (c) and 1500.40, Consumer Product Safety Commission, Federal Hazardous Substances Act Regulations.
Deviations:
not applicable
GLP compliance:
no
Remarks:
Study was performed under the control of a quality assurance unit similar to GLP
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Morton Commercial Rabbits, Parsonage Farm, Stansted, Essex
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Age at study initiation: 3-4 months
- Weight at study initiation: 2.04 - 2.83 kg
- Housing: individually
- Diet:. ad libitum
- Water: ad libitum
- Acclimation period: at least 2 wk

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16+/-2
- Humidity (%): 50-70
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 10/14
Type of coverage:
occlusive
Vehicle:
other: physiologica l saline
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 3times on first day, and twice daily after day 2
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred
Interpretation of results:
study cannot be used for classification
Conclusions:
The acute dermal toxicity of H 48 bleach was >2000 mg/kg bw. in the combined sex.
According to Directive 67/548/EEC and CLP GHS, H 48 bleach requires no classification, as the acute oral LD50 was >2000 mg/kg of body weight.
Executive summary:

The acute dermal toxicity of H 48 bleach was investigated in groups of 5 male and female New Zealand White rabbits after a single dermal administration of 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Guideline study

Additional information

Justification for classification or non-classification

Based on LC50 after inhalation exposure classification as Acute toxicity (Inhalation): Category 4 H332 Harmful if inhaled. is warranted.

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