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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Remarks:
Intraperitoneal injection
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance was injected intraperitoneally in a volume of 10 ml/kg bw .
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Lot no. 447334
- Expiration date of the lot/batch:
- Purity test date:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
- Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material)

OTHER SPECIFICS:

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Chemicals Evaluation and Research Institute (CERI) Tokyo
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing: Individually
- Diet (e.g. ad libitum): During experiments, animals were allowed to access food and water ad libitum.
- Water (e.g. ad libitum): During experiments, animals were allowed to access food and water ad libitum.
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 1°C
- Humidity (%): 55 +/-5%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: Gum arabic saline
Details on exposure:
The test substance was injected intraperitoneally. Ten male rats were assigned to doses of 0 (vehicle control), 751, 826, 909, 1000, and 1100 mg/kg. Ten female rats were assigned to doses of 0 (vehicle control), 683, 751, 826, 909, 1000, and 1100 mg/kg.
Doses:
Ten male rats were assigned to doses of 0 (vehicle control), 751, 826, 909, 1000, and 1100 mg/kg.
Ten female rats were assigned to doses of 0 (vehicle control), 683, 751, 826, 909, 1000, and 1100 mg/kg.
No. of animals per sex per dose:
10
Control animals:
not specified

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
944 mg/kg bw
Based on:
test mat.
95% CL:
>= 859 - <= 1 037
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
874 mg/kg bw
Based on:
test mat.
95% CL:
>= 790 - <= 967
Mortality:
Acute toxicity of p-toluic acid in rats (i.p.)
==================================
Dose Mortality
Sex (mg/kg) (Dead / tested)
----------------------------------
751 0/10
826 1/10
909 3/10
male 1000 7/10
1100 10/10
----------------------------------
683 0/10
751 1/10
826 2/10
female 909 7/10
1000 9/10
1100 10/10
Clinical signs:
No clinical signs were observed in the control animals.
In the treated animals, clinical signs, such as sedation, a decrease in spontaneous locomotion, prone position, limb weakness, abasia, ptosis, lacrimation, nasal hemorrhage, coma, loss of righting reflex, loss of hearing, touch and pain reflex, loss of pinna and corneal reflex, a decrease heart rate, subnormal temperature, deep respiration, bradypnea, respiratory arrest and death, were observed shortly after the injection of p-toluic acid. In the surviving animals, all clinical signs disappeared by Day 5.
Body weight:
Dose-depended suppression of the body weight gain was observed in the females at 751-909 mg/kg bw. The body weight of the other treated animals was approximately equal to that of the control animals.

Gross pathology:
In half of the animals, nasal hemorrhage and reddish tear were observed. In the animals that died within 4 hours after injection, some amount of the test substance still remained at an injection site. In most animals that died within 24 hours after injection, ascites, petechial hemorrhages in the mucosa of small intestine, congestion of the lung, liver and mucosa of small intestine were observed. In the animals that died on the second day after injection and in surviving ones, slight to mild thickening of the quadrate lobe of liver, dull margin of the quadrate lobe and left hepatic lobe, the adhesion between the quadrate and right lobe of the liver and the adhesion between love of liver and the peritoneum were observed

Applicant's summary and conclusion

Conclusions:
Although this intraperitoneal injection study in the rat returned results of LD50 male 944 mg/kg bw and female 874 mg/kg bw, which implies a classification of Acute Toxicity 4, it will not be used for classifcation as this is not an accepted route for human exposure.