2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

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)

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs.

IUPAC Name:

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs.

Constituent 2

Reference substance name:

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs.

EC Number:

274-972-1

EC Name:

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs.

Cas Number:

70879-65-1

Molecular formula:

C23H17N4O

IUPAC Name:

2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs

Details on test material:

- Name of test material : 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs.
- Substance type: Organic
- Physical state: liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Age : 7 to 9 weeks
Sex : Female, nulliparous and non pregnant. It has been observed that females are generally more sensitive than males to toxic effects
Body weight range : 200±20g
Acclimation : One week in experimental room after veterinary examination.
Randomization : After acclimation and veterinary examination randomly selected in groups of three females.
Nutritional conditions : Fasted overnight prior to treatment. Food was offered three hours after dosing.
Environmental conditions :Air conditioned rooms with 10-15 air changes per hour, temperature between 22-25 0C, relative humidity 40-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.

Administration / exposure

Route of administration:

other: oral cannula

Vehicle:

corn oil

Details on oral exposure:

DOSE FORMULATION
Dose preparation of the test article was done freshly, few minutes prior to dosing. Test substance 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs. was mixed corn oil to obtain final concentration of 200 and 30mg/ml.

ADMINISTRATION OF TEST COMPOUND:
The test compound was administered by oral route by using of oral cannula at the dose volume of 10 ml/kg b.wt

Doses:

Two + one vehicle control
Group I : Dist. water, 10ml/kg body wt.
Group II : 2000 mg/kg body wt.
Group III : 300 mg/kg body wt.
Group IV : 300 mg/kg body wt.

No. of animals per sex per dose:

Three (3 females)/step

Control animals:

yes

Details on study design:

STUDY DESIGN:
The toxicity of the test compound following oral administration was assessed. Three female rats were used per step for each dose level. The rats were observed for incidence of mortality and signs of intoxication for 14 days after the administration of test article
OBSERVATION
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.
Histopathological study
The organ which showed gross pathological change during necropsy subjected for histopathological study

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

300 mg/kg bw

Based on:

test mat.

Mortality:

Dose 2000 mg/kg body weight- Test compound produced two mortalities after 24 hrs of administration.
Dose 300 mg/kg body weight- Test compound did not elicit any mortality throughout the period of observation

Clinical signs:

other: Dose 2000 mg/kg body weight- The test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs administered at the dose 2000 mg/kg body weight to wistar albino rats (female) showed moderate to severe clinical signs of toxicity viz; decre

Gross pathology:

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.
1. ABDOMINAL CAVITY
i.Opening and general examination- In the abdominal cavity all the organs were present in normal position.
ii.Spleen- Normal upto highest tested dose level 2000 mg/kg b.wt.
iii.Digestive system- No gross changes were observed in stomach and intestine upto highest tested dose level 2000 mg/kg b.wt.
iv.Liver and biliary ducts- No gross pathological changes were observed
v.Excretory system- No gross pathological changes were observed upto highest tested dose level 2000 mg/kg b.wt.
vi.Adrenal- Observed normal.
vii.Male/female genital organs – Showed normal colour, consistency and no inflammatory changes upto highest tested dose level 2000 mg/kg b.wt.
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 upto highest tested dose level 2000 mg/kg b.wt.
3. CRANIAL CAVITY
i.Brain- Normal in shape and size.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

From the above results it is concluded that the test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs is non-toxic to Wistar albino rats at the tested dose level 300 mg/kg b.wt. According to Globally Harmonized Classification System for Chemical Substances, it comes under the Globally Harmonized Classification (GHS) Category-4 (>300-2000). The cut-off LD50 is estimated to be 1000 mg/kg body weight.

Executive summary:

From the above results it is concluded that the test compound 2-Naphthalenol, 1-[[4-(phenylazo)phenyl]azo]-, ar',ar''-Me derivs is non-toxic to Wistar albino rats at the tested dose level 300 mg/kg b.wt. According to Globally Harmonized Classification System for Chemical Substances, it comes under the Globally Harmonized Classification (GHS) Category-4 (>300-2000). The cut-off LD50 is estimated to be 1000 mg/kg body weight.