Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From June 21, 1988 to July 15, 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable study report, followed basic scientific principles/methods.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Limit Test
Principles of method if other than guideline:
Acute oral toxicity or LD50 value was determined by oral administration of 20% aqueous solution of the test substance to a single dose group (limit dose of 2000 mg/kg bw) of male and female rats. Post-dosing, animals were observed for mortality and signs of toxic and pharmacologic effects for 14 days. The survivors were necropsied after 14 days and observed for gross lesions. The method followed in this study was based on the OECD guideline 401.
GLP compliance:
yes
Remarks:
according to OECD principles of GLP
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material: 2-Amino-6-chloro-4-nitrophenol, Chlororange
- TSIN: COS 198
- Substance type: Pure active substance
- Physical state: Orange- yellow fine grained powder
- Stability under test conditions: Not reported
- Storage condition of test material: Normal room temperature, in darkness

Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Wella AG, n°batch : COS 198
- Expiration date of the lot/batch: No data
- Purity test date: No data
- Purity : 100 area% (HPLC at 254 nm)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: normal room temperature, in darkness
- Stability under test conditions: No data
- Solubility and stability of the test substance in the solvent/vehicle: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING :
- Treatment of test material prior to testing: Yes (dllution)
- Final dilution of a dissolved liquid : 20%

Test animals

Species:
rat
Strain:
other: Crl.:(WI) BR - Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Firma Charles River Wiga, Sandhofer Weg 7, 8714 Sulzfeld
- Age at study initiation: Not reported
- Weight at study initiation: Males : 196 - 228 g; Females : 176 - 205 g
- Fasting period before study: 16 hours before administration of the test sample
- Housing: Collective caging, macrolon type III/max. 5
- Bedding: H-3/4 produced from pure soft wood, dried, disdusted and sterilized at 180°C
- Diet: Pellets (2.4 cm long, 1.0 diameter); Ssniff- R Alleindiet for rats; ad libitum
- Water: Aqua fontana as for human consumption in Macrolon drinking bottles; ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 2 °C
- Humidity: 50 - 80%
- Air changes: Not reported
- Photoperiod: 12 hours daily, from 7.00 a.m. - 7.00 p.m.; fluorescent light, 120 lux

IN-LIFE DATES: From June 21, 1988 to July 15, 1988

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled water
Details on oral exposure:
DOSAGE: The test compound was applied as a 20 % dilution in aqua deion.

TREATMENT: After being fasted for approximately 16 hours, the animals were administered single dose of test substance orally by stomach tube. Food was presented after 4 hours of dosing.

MAXIMUM DOSE VOLUME APPLIED: 2.3 mL

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made at the following intervals: about 20 minutes, 1 +2 h, 3+6 h, 24/48 h, thereafter once daily up to Day 14. The body weights are recorded at Day 0, at Day 7 and at Day 14 on the surviving animals.
- Necropsy of survivors performed: yes, all surviving animals were subjected to complete gross necropsy following their sacrifice at the end of Day 14 or spontaneous death.

RANGE FINDING STUDY: Yes, a range finding study was conducted using 2 female rats at a single dose of 2000 mg/kg bw. No mortality was observed in this range finding study. Based on this result, 2000 mg/kg bw was used as a maximum dosage (limit dose) for the main study.

Statistics:
As no mortality was observed, statistical analysis cannot be performed.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortalities were observed
Clinical signs:
Red-orange-stained bedding (urines red-orange-stained) was observed up to 5 days
Body weight:
Normal weight gain was observed
Gross pathology:
No macroscopic findings were observed in the cranial, thoracic and abdominal cavity.
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity (LD50) of Chlororange (2-Amino-6-chloro-4-nitrophenol) was > 2000 mg/kg bw in male and female rats. Therefore, this test substance is not classified according to EU criteria for classification.
Executive summary:

The objective of this study was to determine the acute oral toxicity (LD50) of Cholorange (2-Amino-6-chloro-4-nitrophenol) when administered once orally to male and female rats.Crl.:(WI) BR - Wistar rats.

Ten animals (5 males and 5 females) obtained from Firma Charles River Wiga, Sandhofer Weg 7, 8714 Sulzfeld were used in this study. The animals were housed in groups of 5 in Makrolon type-3 cages with standard softwood bedding. Pelleted Ssniff- R Alleindiet and aqua fontana water were provided ad libitum. The animals were maintained according to standard laboratory conditions (temperature: 20 ± 2°C, relative Humidity: 50 – 80%, photoperiod: 12 h artificial fluorescent light/12 h dark). Animals were acclimated for one week and fasted for 16 h prior to dosing.

The test substance was administered as a 20% dilution in aqua deion to animals orally by stomach tube at a limit dose of 2000 mg/kg bw.

Post treatment, animals were examined for mortality and clinical signs at about 20 minutes, 1h, 2 h, 3h, 6 h, 24h, 48 h and thereafter once daily up to Day 14. Body weights were recorded on Day 0, Day 7 and on Day 14. After 14 days of observation, all surviving animals were subjected to complete gross necropsy following their sacrifice at the end of Day 14 or spontaneous death. No mortality was observed during the study. Red-orange-stained bedding (urines red-orange-stained) was observed up to 5 days post administration.Body weights changes after each observation period showed a normal weight gain. No macroscopic findings were noted during necropsy.

Based on above, the acute oral toxicity (LD50) of Cholorange was determined to be > 2000 mg/kg bw. Therefore, this test substance is not classified according to EU criteria for classification.