3-aminophenol

Acute Toxicity: oral

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:

guideline study

Justification for type of information:

Data is from study report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

Acute oral toxicity of test chemical in rats

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-aminophenol

EC Number:

209-711-2

EC Name:

3-aminophenol

Cas Number:

591-27-5

Molecular formula:

C6H7NO

IUPAC Name:

3-aminophenol

Test material form:

solid: crystalline

Details on test material:

- Name of test material: 3-aminophenol
- IUPAC name: 1-Hydroxy-3-amino-benzene
- Molecular weight: 109.127 g/mole
- Molecular formula: C6H7NO
- Smiles: c1c(cccc1O)N
- InChI: 1S/C6H7NO/c7-5-2-1-3-6(8)4-5/h1-4,8H,7H2
- Substance type: Organic
- Physical state: Solid Crystalline (white)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Institute for Industrial Research & Toxicology
- Age at study initiation: 7 to 9 weeks
- Weight at study initiation: 200±20g
- Fasting period before study: Fasted overnight prior to treatment. Food was offered three hours after dosing
- Housing: Groups of three animals of similar sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle, and bedding of clean paddy husk
- Diet (e.g. ad libitum): Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India
- Water (e.g. ad libitum): Aqua Guard filter water was kept in PVC bottles, ad libitum
- Acclimation period: One week in experimental room after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25° C
- Humidity (%): 40-60%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on oral exposure:

Dose preparation of the test article was done freshly, few minutes prior to dosing. Test substance was dissolved in distilled water to obtain final concentration of 200mg/ml.

Doses:

Group I: Dist. water, 10ml/kg body wt.
Group II: 2000 mg/kg body wt.
Group III: 2000 mg/kg body wt
The test compound was administered by oral route by using of oral cannula at the dose volume of 10 ml/kg b.wt.

No. of animals per sex per dose:

Three + one vehicle control

Control animals:

yes

Details on study design:

Body weight:
The body weight of all the animals was observed weekly on day 0 (pre treatment), 7th and 14th (post treatment).
Mortality:
The test compound was administered at different dose level in wistar albino rats observed for mortality at the time interval of 30 minutes, 1hr, 2hr, 4 hr, and 6hr time interval on the day of test compound administration and thereafter twice a day for 14 days.
Clinical Signs
The treated animals were closely observed for clinical signs of intoxication, first 4 hours and every 1 hrs interval for 24 hrs after dosing and thereafter twice a day for 14 days. All the rats were observed at least twice daily to observe any clinical signs or behavioral changes. These observations included changes in skin and fur, in the eyes and mucous membranes, respiratory, circulatory, central nervous and autonomic nervous systems, somatomotor activity and behavioral changes. The following clinical signs were observed in female mice to characterize the various systemic studies: Salivation, lacrimation, pale mucous membrane, diarrheal feaces, hunched posture, scratching, polyuria, hypoactivity etc. The clinical sign will be graded as 0 = Normal, + = Mild, ++= Moderate, +++ =High and ++++ = Severe.
Necropsy:
Necropsy was carried out on all the animals which died during the study or surviving animals were sacrificed at the end of the study to observe any gross pathological changes.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test compound administered at the dose level of 2000 mg/kg b.wt did not elicit any mortality throughout the observation period of 14 days

Clinical signs:

other: Test compound did not produce any clinical signs of intoxication in wistar albino rats throughout the observation period of 14 days at the dose level of 2000 mg/kg b.wt.

Gross pathology:

NECROPSY FINDING
ABDOMINAL CAVITY
i. Opening and general examination- In the abdominal cavity all the organs were present in normal position.
ii. Spleen- Normal at 2000 mg/kg b.wt.
iii. Digestive system- No gross changes were observed.
iv. Liver and biliary ducts- No gross pathological changes were observed
v. Excretory system- No gross pathological changes were observed at the dose level of 2000 mg/kg b.wt.
vi. Adrenal- Observed normal.
vii. Male/female genital organs – Showed normal colour, consistency and no inflammatory changes.
2. THORACIC CAVITY
i. Opening and general examination- Thoracic cavity was found to be normal without any fluid, mucous or blood etc.
ii. Lungs- observed normal.
iii. Heart- No changes were observed in color and consistency. Heart found normal upto highest tested dose level 2000 mg/kg b.wt.
iv. Thyroid- Normal in shape, size and surface.
3. CRANIAL CAVITY
i. Brain- Normal in size and no gross pathological changes were observed.

Other findings:

NECROPSY FINDING
EXTERNAL
i. Skin- Skin and hair coat was observed wet.
ii. All external orifices- Normal
B. INTERNAL
i. Subcutaneous- No change was observed.
ii. Superficial and deep lymph nodes- No change in mesenteric lymph node.

Any other information on results incl. tables

Table:SUMMARY OF BODY WEIGHT (GM)

Group	Day 0	Day 7	% Gain/loss	Day 14	% Gain/loss
Group-I Distilled water 10ml/kg	203.34	209.66	2.96	213.5	5.0
Group-II 2000 mg/kg b. wt	201.25	208.19	3.44	215.21	6.93
Group-III 2000 mg/kg b. wt	202.76	207.58	2.37	216.41	6.73

TABLE :

CLINICAL SIGNS AND MORTALITY

Group: I (Vehicle Control)                                                           Dose: 10 ml/kg b.wt

FEMALE RATS

Parameters	Incidence of clinical signs observed after dosing																			Mortality
	Day 0					DAY
	Min	Hour
	30	1	2	4	6	1	2	3	4	5	6	7	8	9	10	11	12	13	14	Total^*
Mortality (total)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/3
Clinical Signs	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0            =   Normal

+            =    Mild

++           =   Moderate

+++         =    High

++++ =        Severe

TABLE :

CLINICAL SIGNS AND MORTALITY

Group: II                                                                                           Dose: 2000 mg/kg b. wt.

 

FEMALE RATS

Parameters	Incidence of clinical signs observed after dosing																			Mortality
	Day 0					DAY
	Min	Hour
	30	1	2	4	6	1	2	3	4	5	6	7	8	9	10	11	12	13	14	Total^*
Mortality (total)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/3
Clinical Signs	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0            =   Normal

+            =    Mild

++           =   Moderate

+++         =    High

++++      =   Severe

TABLE :

SUMMARY OF NECROPSY FINDINGS

 

S. No.	Fate	Wistar albino rats
		Dose (mg/kg b. wt)
		Distilled water (10 ml/kg)	2000	2000
1	Terminal sacrifice	3/3	3/3	3/3
2	Found Dead	0/3	0/3	0/3
3	Abnormalities detected	NAD	NAD	NAD

 

NAD - No abnormality recorded

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

Based on the results obtained from present investigation, it can be concluded that the test chemical is non- toxic to wistar albino rats at the dose level of 2000 mg/kg b.wt.

Executive summary:

Acute oral toxicity study of test chemical was conducted in 3 female Wistar rats at the dose concentration of 2000mg/kg bw. Test chemical was administered through oral cannula at a dose level of 10ml/Kg bw with distill water as a vehicle. The rats were observed for 14 days for mortality and body weight changes. No mortality was observed at 2000 mg/kg bw. Hence,LD50 value was considered to be >2000 mg/kg bw, when 3 female Wistar rats were treated with test chemical by oral route.