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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from publication.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
acute toxicity
Author:
Lloyd et al.
Year:
1977
Bibliographic source:
Food and Cosmetics Toxicology
Reference Type:
publication
Title:
IARC MONOGRAPHS
Author:
IARC
Year:
1993
Bibliographic source:
IARC
Reference Type:
review article or handbook
Title:
Acute oral toxicity of test chemical
Author:
Richard J. Lewis
Year:
2012
Bibliographic source:
Sax's Dangerous Properties of Industrial Materials
Reference Type:
review article or handbook
Title:
Acute oral toxicity - Test chemical in rodent
Author:
S D Gangolli
Year:
2007
Bibliographic source:
The Dictionary of Substances and their Effects (DOSE)
Reference Type:
other: authoritative database
Title:
Acute oral toxicity by using test chemical
Author:
U.S. National Library of Medicine
Year:
2018
Bibliographic source:
ChemIDplus
Reference Type:
publication
Title:
Acute oral toxicity of test chemical
Author:
IFA GESTIS
Year:
2018
Bibliographic source:
IFA GESTIS
Reference Type:
other: authoritative database
Title:
Acute Toxicities of the given test chemical
Author:
U.S. National Library of Medicine
Year:
2008
Bibliographic source:
HSDB
Reference Type:
secondary source
Title:
HUMAN HEALTH TIER II ASSESSMENT
Author:
NICNAS
Year:
2018
Bibliographic source:
INVENTORY MULTITIERED ASSESSMENT AND PRIORITISATION (IMAP) NICNAS

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Acute oral toxicity study of the given test chemical in rat.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- IUPAC Name: 2-amino-4-nitrophenol
- InChI: 1S/C6H6N2O3/c7-5-3-4(8(10)11)1-2-6(5)9/h1-3,9H,7H2
- Smiles: Nc1cc(ccc1O)[N+](=O)[O-]
- Molecular formula :C6H6N2O3
- Molecular weight :154.1244 g/mol
- Substance type:organic
- Physical state:Solid, powder yellow

Test animals

Species:
rat
Strain:
other: CFY strain
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: weight range 90-122 g
- Fasting period before study: The animals were starved overnight before treatment.

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: Aqueous solution or suspension in 0.5% aqueous gum tragacanth
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40%
- DOSAGE PREPARATION (if unusual): The test material was prepared as aqueous solution or suspension in 0.5% aqueous gum tragacanth containing 0.05% Na2SO3.
Doses:
Range of 2000 - 3000 mg/kg bw
No. of animals per sex per dose:
five males and five females per groups of rats
Control animals:
yes
Remarks:
Rats treated with the vehicle alone served as controls
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During the observation period of 14 days, a record was kept of all deaths and signs of toxicity.
- Necropsy of survivors performed: yes, all rats that died were examined macroscopically in an attempt to identify the target organs, and animals surviving to the end of the experiment were similarly examined at that time to detect any possible residual damage. There was no microscopic examination of the various tissues and organ systems.
Statistics:
The LD50 and its 95% confidence limits were calculated from the mortality data either by the method of Litchfield & Wilcoxon (1949) or by that of Weil (1952).

Results and discussion

Preliminary study:
In a preliminary range finding study, the freshly prepared solutions or suspensions were administered to groups of two male and two female rats by oral intubation in a range of dosage volumes, in order to find the approximate median lethal oral dose (LD50).
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 400 mg/kg bw
Based on:
test mat.
95% CL:
2 000 - 3 000
Mortality:
50% mortality was observed at 2400 mg/kg bw in treated animals.
Clinical signs:
Signs of reaction to treatment, observed shortly after dosing with the compound, included lethargy and piloerection. Other reactions included increased salivation, ataxia, fine body tremors, changes in respiratory rate, dieresis and diarrhea. Also, produced orange-stained urine. These signs were not considered to be indicative of any specific target-organ toxicity.
Body weight:
not specified
Gross pathology:
Autopsy of the animals that died as a result of treatment revealed changes which, in many cases, included darkening of the liver and kidneys, darkening or pallor of the spleen, hemorrhage of the lungs and intestines, and injection of the intestinal and mesenteric blood vessels. Also, the rats showed orange staining of the peritoneal wall.
Autopsy of the survivors at the end of each experiment did not reveal any abnormalities indicative of residual systemic effects.
Other findings:
not specified

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
The acute oral LD50 value was considered to be 2400 mg/kg bw, with 95% confidence limit of 2000 - 3000 mg/kg bw, when groups of rats (five males and five females) were treated with the given test chemical via oral route.
Executive summary:

Acute oral toxicity study of the given test chemical was conducted in groups of rats (five males and five females) at the dose concentration range of 2000 - 3000 mg/kg bw.

The given test chemical was prepared as aqueous solution or suspension in 0.5% aqueous gum tragacanth, containing 0.05% Na2SO3 and administered via oral route. Rats treated with the vehicle alone served as control.

In a preliminary range finding study, the freshly prepared solutions or suspensions were administered to groups of two male and two female rats by oral intubation in a range of dosage volumes, in order to find the approximate median lethal oral dose (LD50).

After these preliminary range-finding tests had given a rough approximation of the LD50, larger groups of rats (five males and five females) were used in order to locate the median lethal dose more precisely. A logarithmic dosage interval of 1.6 was used for material.

During the observation period of 14 days, a record was kept of all deaths and signs of toxicity. Necropsy of survivors performed. All rats that died were examined macroscopically in an attempt to identify the target organs, and animals surviving to the end of the experiment were similarly examined at that time to detect any possible residual damage. There was no microscopic examination of the various tissues and organ systems.

The LD50 and its 95% confidence limits were calculated from the mortality data either by the method of Litchfield & Wilcoxon (1949) or by that of Weil (1952).

50% mortality was observed at 2400 mg/kg bw in treated animals. Signs of reaction to treatment, observed shortly after dosing with the compound, included lethargy and piloerection. Other reactions included increased salivation, ataxia, fine body tremors, and changes in respiratory rate, dieresis and diarrhea. Also, produced orange-stained urine. These signs were not considered to be indicative of any specific target-organ toxicity.

Autopsy of the animals that died as a result of treatment revealed changes which, in many cases, included darkening of the liver and kidneys, darkening or pallor of the spleen, hemorrhage of the lungs and intestines, and injection of the intestinal and mesenteric blood vessels. Also, the rats showed orange staining of the peritoneal wall. Autopsy of the survivors at the end of each experiment did not reveal any abnormalities indicative of residual systemic effects.

Under the condition of the study, the LD50 value was considered to be 2400 mg/kg bw, with 95% confidence limit of 2000 - 3000 mg/kg bw, when groups of rats (five males and five females) were treated with the given test chemical via oral route.