2-amino-4,6-dinitrophenol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Data source

Reference

Reference Type:

secondary source

Title:

OPINION ON Picramic acid and sodium picramate COLIPA n° B28

Author:

Scientific Committee on Consumer Safety

Year:

2012

Bibliographic source:

Scientific Committee on Consumer Safety, (SCCS) 18 September 2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

To evaluate the acute toxicity of picramic acid in CFY rats.

GLP compliance:

not specified

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-4,6-dinitrophenol

EC Number:

202-544-6

EC Name:

2-amino-4,6-dinitrophenol

Cas Number:

96-91-3

Molecular formula:

C6H5N3O5

IUPAC Name:

2-amino-4,6-dinitrophenol

Test material form:

other: Dark red needles

Details on test material:

- Name of test material (as cited in study report): Picramic acid
- Molecular formula (if other than submission substance): C6H5N3O5
- Molecular weight (if other than submission substance): 199.125g\mol
- Substance type: Organic
- Physical state: Dark red needles
- Purity No data available.
- Impurities (identity and concentrations): No data available.

Test animals

Species:

rat

Strain:

other: CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: NO data available.
- Age at study initiation: NO data available.
- Weight at study initiation: 95 to 120 g
- Fasting period before study: Starved overnight before treatment
- Housing: NO data available.
- Diet (e.g. ad libitum): NO data available.
- Water (e.g. ad libitum): NO data available.
- Acclimation period: NO data available.

ENVIRONMENTAL CONDITIONS
No data available.

IN-LIFE DATES: From: To: NO data available.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 10% suspension in aqueous gum tragacanth (0.5%) containing 0.05% sodium sulfite.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0, 100, 160, 250, 400 and 640 mg/kg bw
- Amount of vehicle (if gavage): 10%suspension in aqueous gum tragacanth (0.5%) containing 0.05% sodium sulfite.
- Justification for choice of vehicle: No data available.
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: No data available.
DOSAGE PREPARATION (if unusual): Picramic acid was prepared as a 10% suspension in aqueous gum tragacanth (0.5%) and administered by oral intubation at a range of dosage volumes of 1.0 to 6.4 ml/kg bw, corresponding to doses from 100 to 640 mg/kg bw.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The results of preliminary range finding tests indicated that the median lethal oral dose (LD5O), was in the region of 100 to 400 mg/kg bw. Dosing was then extended to larger groups of rats (five males and five females) in order to set the median lethal dose more precisely.

Doses:

0, 100, 160, 250, 400 and 640 mg/kg bw

No. of animals per sex per dose:

0 mg/kg bw- 5 males and 5 females
100 mg/kg bw- 5 males and 5 females
160 mg/kg bw - 5 males and 5 females
250 mg/kg bw - 5 males and 5 females
400 mg/kg bw - 5 males and 5 females
640 mg/kg bw-- 5 males and 5 females

Control animals:

yes

Details on study design:

Control animals: Yes ,concurrent vehicle.( Rats treated with the vehicle alone (6.4 ml/kg bw) served as controls
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: From1st of the treatment to the 14 day of treatment.
- Necropsy of survivors performed: yes, All rats that died were examined macroscopically to identify the target organs and surviving animals were similarly examined after the observation period to detect possible damage.
- Other examinations performed: Mortality,clinical signs, body weight, organ weights and gross pathology were observed.

Statistics:

No data available

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

110 mg/kg bw

Based on:

test mat.

95% CL:

63 - 176

Mortality:

Mortality was observed from within one to 19 hours of treatment.

Clinical signs:

other: Signs of reactions to treatment were observed shortly after dosing, including lethargy, piloerection and orange staining of external extremities. These signs were accompanied within five hours by gasping in six rats treated at 100 mg/kg bw. Recovery of su

Gross pathology:

Autopsy revealed discoloration of the liver, pallor of the kidneys and spleen, and orange staining of the inner body wall.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 was found to be 110 mg/kg bw for Picramic acid in CFY male and female rats.

Executive summary:

In acute oral median lethal dose (LD50) for Picramic acid was determined in CFY male and female rats. Signs of reactions to treatment were observed shortly after dosing, including lethargy, piloerection and orange staining of external extremities. These signs were accompanied within five hours by gasping in six rats treated at 100 mg/kg bw.

Death occurred from within one to 19 hours of treatment. Autopsy revealed discoloration of the liver, pallor of the kidneys and spleen, and orange staining of the inner body wall. Recovery of survivors, as judged by external appearance and behaviour was apparently complete within five days after treatment. Bodyweight gains were within normal limits compared with controls and normal autopsy findings.

The acute median lethal oral dose (LD50) and its 95% confidence limits to CFY male and female rats of picramic acid were calculated to be 110 (63-176) mg/kg bw.