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Toxicological information

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Experimental result performed using standard test methods

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
To assess the acute oral toxicity potency of test chemical when exported to rats via oral route
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Off white crystalline powder
Details on test material:
- Name of test material (as cited in study report): tert-butyl-4-methoxyphenol
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals 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 0.1% Tween 80 in distilled water to obtain final concentration of 200 mg/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
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no other details available
Mortality:
The test compound administered at the dose level of 2000 mg/kg b.wt. did not show any mortality throughout the observation period
Clinical signs:
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.
Body weight:
All the animals treated with the test compound CAS No. 25013-16-5 at the dose level of 2000 mg/kg b.wt on day 7th and 14th showed normal gain in body weight as compared to control group
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.
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.

Applicant's summary and conclusion

Interpretation of results:
not classified
Conclusions:
Under the condition of the study, the acute oral LD50 value of test chemical was considered to be >2000 mg/kg body weight. Thus, it was concluded that the acute toxicity study of test chemical when administered via oral route in Wistar rats falls into the “Category Not classified” criteria of CLP.
Executive summary:

The reported study was designed and conducted to determine the acute oral toxicity profile test chemical in wistar rats. The study was conducted in accordance with OECD guideline 423 for testing of chemicals. Initially, three female animals were treated at the dose level of 2000 mg/kg body weight of the test item (Step - I). Administration of the test item at 2000 mg/kg did not result in any signs of toxicity and mortality throughout the observation period.No clinical sings and mortality were observed in vechicle group.The necropsy was conducted on all the animals at the termination of the study did not reveal any gross pathological changes .After 72hours ,the result of step I was confirmed by administration of same dose level of the test chemical in additional three animals of same sex.

It is concluded that test chemical following the guideline OECD-423 is non-toxic to Wistar albino rats at the dose level of 2000 mg/kg bw.According to Globally Harmonized system of classification,the chemical is considered as “Not classified”