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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
Study period:
2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well performed OECD study with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity: 97.8 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
Animal Breeding, RCC Laboratories India Private Limited, Genome Valley, Turkapally, Shameerpet (Mandal), Ranga Reddy District, Hyderabad - 500 078, India
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 147.4 - 153.9 g
- Housing:
Housed in groups of three in polycarbonate cages (approximate internal dimensions of 365 mm x 202 mm x 180 mm height) with paddy husk bedding
- Fatsing period: 17.h hours
- Diet: Nutrilab rodent feed from Provimi Animal Nutrition India Pvt. Ltd ( ad libitum):
- Water: Aquaguard filtered tap water ( ad libitum):
- Acclimation period: Under laboratory conditions for 5 and 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 - 21.5
- Humidity (%): 57 - 67
- Air changes (per hr): more than 10
- Photoperiod (hrs dark / hrs light): light cycle of 12 hours light and 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Refined groundnut oil
Details on oral exposure:
2000 mg / 10 ml (w/v)
Doses:
2000 mg/kg bw corresponds to 10 ml mixture/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
Three female rats received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight at Step I. No mortality was observed in three out of three animal dosed at 2000 mg/kg body weight (Step I), three naive female rats were again treated at the same dose of 2000 mg/kg body weight (Step II), as there was no mortality at Step II and all the treated animals of Step I and Step II survived throughout the experimental period, no further testing was carried out.

- Duration of observation period following administration: 14 days

OBSERVATIONS
Mortality / Viability: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 4 hours after administration on test day 0 (in common with the clinical signs) and twice daily during days 1-14 (at least once on holidays and days of sacrifice).
Body weights: On test days 0 (prior to administration), day 7 and day 14.
Clinical signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 4 hours after administration on te st day 0. Once daily during days 1-14.
Statistics:
No statistical analysis was used

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed
Clinical signs:
All the animals of Step I (Animal No. 01, 02 and 03) and Step II (Animal No. 04, 05 and 06) treated at 2000 mg/kg body weight appeared normal at first 30 minutes of observation on day 0 after treatment. At 1 hour and 2 hour observation, all the treated animals of Step I and Step II exhibited dullness and Piloerection, all the treated animals continued to exhibit dullness at 3 hour and 4 hour observation on day 0. On day 1 observation, all the treated animals of Step I (Animal No. 01, 02 and 03) continued to exhibit dullness whereas all the treated animals of Step II (Animal No. 04, 05 and 06) appeared normal. All the treated animals of Step I (Animal No. 01, 02 and 03) and Step II (Animal No. 04, 05 and 06) appeared normal form day 2 till the end of the last observation period (day 14).
Body weight:
All surviving animals had gained body weight by day 7 and 14 as compared to day 0
Gross pathology:
No abnormalities were observed in any of the treated animals at terminal sacrifice

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Since no mortality and since only temporary, unspecific clinical signs but no significant signs of toxicity were observed at 2000 mg/kg body weight, the higest dose tested, the LD50 was determined to be greater than 2000 and is anticipated to be greater than 5000 mg/kg body weight.
Executive summary:

Two groups, each of three female Wistar rats, were treated with Methyl p-toluate by oral gavage administration at a dosage of 2000 mg/kg body weight for Step I and Step II. The test item was formulated in vehicle (Refined groundnut oil) at a concentration of 200 mg/mL for Step I, II and administered at a dose volume of 10 mL/kg body weight.

The animals were observed daily during the acclimatization period, mortality/viability and clinical signs were recorded. All the animals were observed for clinical signs during first 30 minutes and at approximately 1, 2, 3 and 4 hours after administration on test day 0 and once daily during test days 1‑14. Mortality/viability was recorded during first 30 minutes and at approximately 1, 2, 3 and 4  hours after administration on test day 0 (in common with the clinical signs) and twice daily during days 1-14 (once on day of sacrifice). Body weights were re­corded on test day 0 (prior to administration), test days 7 and 14. All the animals were necropsied and examined macroscopically.

The following animals were treated as follows:

Step I                3 females treated at 2000 mg/kg                     Mortality 0‘out of 3’

Step II              3 females treated at 2000 mg/kg                     Mortality 0‘out of 3’

All the animals appeared normal throughout the acclimatization period.

All the animals of Step I (Animal No. 01, 02 and 03) and Step II (Animal No. 04, 05 and 06) treated at 2000 mg/kg body weight appeared normal at first 30 minutes of observation on day 0 after treatment. At 1 hour and 2 hour observation, all the treated animals of Step I and Step II exhibited dullness and Piloerection, all the treated animals continued to exhibit dullness at 3 hour and 4 hour observation on day 0. On day 1 observation, all the treated animals of Step I (Animal No. 01, 02 and 03) continued to exhibit dullness whereas all the treated animals of Step II (Animal No. 04, 05 and 06) appeared normal. All the treated animals of Step I (Animal No. 01, 02 and 03) and Step II (Animal No. 04, 05 and 06) appeared normal form day 2 till the end of the last observation period (day 14).

All the animals had gained body weight by day 7 and day 14 as compared to day 0.

No abnormalities were observed in any of the treated animals at terminal sacrifice.