Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to GLP and valid study methods, therefore the study is considered adequate, reliable and relevant for classification.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Chloramin B; sodium N-chlorobenzenesulphonamide trihydrate
- Substance type: Biocide
- Physical state: White to light yellow powder
- Analytical purity: 98%
- Impurities (identity and concentrations): 0.6% NaOH.
- Composition of test material, percentage of components: 77% CAS 127-52-6, 22.4% Water incl. trihydrate), 0.6% NaOH
- Isomers composition: Not applicable
- Purity test date: No data
- Lot/batch No.: 54/MA/20/06
- Expiration date of the lot/batch: 03/2011
- Stability under test conditions: Stable, c.f. Chapter 4.18.
- Storage condition of test material: Stable, c.f. Chapter 4.18.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Breeding farm BioTest s.r.o., Konárovice, 281 25, CZ, RČH CZ 21760152
- Age at study initiation: 7-9 weeks at the time of application
- Weight at study initiation: Range at delivery: 150-170 g
- Fasting period before study: About 20 hours before oral administration the animals were not fed, water was given ad libitum. The feed was given to animals 3 hours after application of the test substance.
- Housing: Animal room with monitoring conditions; 3 animals of one sex in one plastic breeding cage Velaz T4; sterilized shavings of soft wood as bedding
- Diet (e.g. ad libitum): ST 1 BERGMAN standard pelleted diet ad libitum (producer: Mill Kocanda,
Jesenice u Prahy)
- Water (e.g. ad libitum): Drinking tap water ad libitum (quality corresponding to Regulation No. 252/2004 Czech Coll. Of Law)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C (permanently monitored)
- Humidity (%): 30-70% (permanently monitored)
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25-4-2006 To: 18-5-2006

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: water for injection
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Dependent on dose group


MAXIMUM DOSE VOLUME APPLIED: The volume administered solution did not exceed 2mL/100 g of body weight of animals.

DOSAGE PREPARATION (if unusual): Immediately before application the test substance was weighed, mixed in vehicle (water) and administered in a single dose by tube to the stomach.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No rationale for selection of 2000mg /kg bw starting dose
Doses:
2000 mg/kg bw (step 1) and 300 mg/kg bw (step 2 and step 3)
No. of animals per sex per dose:
3 (2 groups dosed at 300 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weight: Before application, the 8th day and before euthanasia of animals
Mortality: Daily
Clinical examination: Daily (on the first day twice (30 minutes and 3 hours after application); on the second day: twice (in the morning an in the afternoon) and daily thereafter for 14 days)
Observations included changes in skin and fur, eyes, visible mucous membranes, behavior of animals, somatomotor activity, reactions to stimuli, presence of lacrimation, salivation and discharge from nostrils, function of respiratory, digestive and urogenital system.
- Necropsy of survivors performed: yes. Nutritious status, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test substance administered at the dose of 2000mg/kg bw caused death of all three animals. The test substance administered at the dose of 300 mg/kg bw caused no death in females.
Clinical signs:
Clinical signs of intoxication were observed in all three animals at the dose of 2000mg/kg bw . Very mild clinical signs of intoxication were observed in three animals (erected hair, hunched posture) at the dose of 300 mg/kg bw.
Body weight:
Body weight increments were adequate to species, sex and age of animals in experiment.
Gross pathology:
Macroscopic changes were diagnosed during pathological examination in all three animals at the dose of 2000 mg/kg bw (Stomach: dilatation, hyperaemia, acute catarrhal inflammation ; Small intestine: acute catarrhal inflammation) and at the dose of 300 mg/kg bw (Liver: dystrophia ).

Any other information on results incl. tables

TABLE 1.    TABLE FOR ACUTE TOXICITY

Animal No.

Animal weight    (g)

Weight increment (g)

Clinical examination

Pathological examination

Step No. 1 (Dose – 2000 mg/kg)

1

155.43

-

30 minutes: erected hair, anaemic cutis and anaemic mucous membrane, abdominal position, immobility, gasping, no reaction to stimulation

2.5 hours: death

Stomach – dilatation, hyperaemia, acute catarrhal inflammation

Small intestine - acute catarrhal inflammation

2

160.16

-

30 minutes: erected hair, anaemic cutis and anaemic mucous membrane, abdominal position, immobility, gasping, no reaction to stimulation

2.5 hours: death

Stomach – dilatation, hyperaemia, acute catarrhal inflammation

Small intestine - acute catarrhal inflammation

3

157.95

-

30 minutes: erected hair, anaemic cutis and anaemic mucous membrane, abdominal position, immobility, gasping, no reaction to stimulation

2.5 hours: death

Stomach – dilatation, hyperaemia, acute catarrhal inflammation

Small intestine - acute catarrhal inflammation

Step No. 2 (Dose – 300 mg/kg)

1

184.33

52.08

30 minutes: no clinical signs of intoxication

3 hours: no clinical signs of intoxication

2nd– 14th day: no clinical signs of intoxication

Liver - dystrophia

2

160.75

42.03

30 minutes: no clinical signs of intoxication

3 hours: no clinical signs of intoxication

2nd– 14th day: no clinical signs of intoxication

Liver – dystrophia

3

180.31

49.46

30 minutes: no clinical signs of intoxication

3 hours: no clinical signs of intoxication

2nd– 14th day: no clinical signs of intoxication

Liver – dystrophia

Step No. 3 (Dose – 300 mg/kg)

1

163.43

45.74

30 minutes: no clinical signs of intoxication

3 hours: no clinical signs of intoxication

2nd– 14th day: no clinical signs of intoxication

No alterations

2

169.46

38.53

30 minutes: no clinical signs of intoxication

3 hours: no clinical signs of intoxication

2nd– 14thday: no clinical signs of intoxication

No alterations

3

168.89

54.62

30 minutes: no clinical signs of intoxication

3 hours: no clinical signs of intoxication

2nd– 14th day: no clinical signs of intoxication

No alterations

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 of the test substance Chloramin B for rats is in the range > 300 mg/kg bw to ≤ 2000 mg/kg bw.
The exact value was not given in the report, but can be considered to be around 1150 mg/kg bw.
Executive summary:

Chloramin B was administered via oral gavage in a single dose as a solution in water for injection. The dosing was performed sequentially in three groups of three females: group No. 1 (first step) using the starting dose of 2000 mg/kg bw, group No. 2 (second step) and group No. 3 (third step) using a dose of 300 mg/kg bw. The dose volume of administered solution did not exceed 2mL/100g bw of animals.
The test substance administered at the dose of 2000 mg/kg bw caused death of all three animals, clinical signs of intoxication were observed in all three animals and macroscopic changes were diagnosed during pathological examination in all three animals.
The test substance administered at the dose of 300 mg/kg bw caused no death in females, very mild clinical signs of intoxication were observed in three animals (erected hair, hunched posture) and macroscopic changes were diagnosed during pathological examination in three females. According to the study results the value of LD50of the test substance Chloramin B for rats is in the range > 300 mg/kg bw to ≤ 2000 mg/kg bw. The exact value was not given in the report, but can be considered to be around 1150 mg/kg bw.