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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data are given.

Data source

Reference
Reference Type:
publication
Title:
Toxicological studies on p-tertiary-butyltoluene.
Author:
Hine CH et al.
Year:
1954
Bibliographic source:
AMA Arch Ind Hyg Occup Med 9: 227-244.

Materials and methods

Principles of method if other than guideline:
No reference is cited for the method used. The test procedure is described very briefly in the publication.
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-tert-butyltoluene
EC Number:
202-675-9
EC Name:
4-tert-butyltoluene
Cas Number:
98-51-1
Molecular formula:
C11H16
IUPAC Name:
1-tert-butyl-4-methylbenzene
Details on test material:
- Name of test material (as cited in study report): p-tertiary-butyltoluene
- Physical state: liquid with distinct odour
- Analytical purity: no data
No further data

Test animals

Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
male Long-Evans rats
- Weight at study initiation: 100 - 145 g
no further data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
other: intragastrically
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
no further details
Doses:
ca. 690, 1030, 1380, 1720, 2070 mg/kg bw (0.8, 1.2, 1.6, 2.0, 2.4 ml/kg bw)
No. of animals per sex per dose:
10 males per group
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 10 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, gross pathology and histopathology of decedents
Statistics:
LD50 was calculated by the method of Miller LC and Tainter ML (1944). Estimation of the ED50 and Its Error by Means of Logarithmic-Probit Graph Paper. Proc Soc Exp Biol Med 57: 261-264.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1 550 mg/kg bw
Remarks on result:
other: Original value: LD50 = 1.8 +/- 0.14 ml/kg bw.
Mortality:
see table 2.
Clinical signs:
The rats receiving the higher dose levels were usually affected within 10 to 15 minutes; those receiving the lower doses were not appreciably affected until 30 minutes had passed. Signs of disturbance of the central nervous system predominated. At first there was stimulation; increase in activity was followed shortly by ataxia, confusion, tolerance of side-position, and marked depression. Dyspnea was apparent early but was not severe until the terminal stages. General paresis, followed by recovery in four or five hours, was observed in several rats. Respiratory depression, accompanied by fibrillation and abnormal posture, usually ended in death. Deaths occurred after 24 to 48 hours.
Body weight:
no data
Gross pathology:
The results of gross pathology are described in a generalized manner.
Gross lesions were present in the majority of animals which showed intoxication and survived for 10 or more hours and were invariably present in moribund animals which survived for 24 hours. These lesions consisted of cerebral edema, engorgement of the abdominal viscera, hyperemia of the .gastrointestinal tract and enlargement and yellowish discoloration of the liver. Slight irritation of the respiratory tract was also seen.
Other findings:
- Histopathology:
The results of microscopic examination are presented for a battery of studies conducted with several species (rat, mouse and rabbit) and several routes of administration (oral, by inhalation, and dermal) and are presented here as a quotation.
“Microscopic examination of the tissues confirmed the extent of visceral involvement and disclosed a number of lesions in the central nervous system. The changes in the liver were principally due to fatty infiltration, which was either centrilobular or diffuse. In the tubular epithelium of the kidneys there were fine granular changes and moderate fatty deposits at the base. Pulmonary emphysema was conspicuous, and in some animals there was diffuse pulmonary edema and severe hemorrhage. All organs were hyperemic.
The lesions of the central nervous system […] may be summarized as follows: In cerebrum, cerebellum, and cord, there was diffuse edema of the white matter and occasionally acute necrosis, particularly in the corpus callosum and the cord. In many areas large vacuoles had formed which contained palely staining material of colloid-like appearance. Acute neuronal changes were present-swelling, vacuolation, and chromatolysis in the cortex, hippocampus, and cerebellum. In the spinal cord, beginning in the medulla oblongata, the nerve cells in the anterior gray columns frequently showed vacuolar changes of nuclei and occasionally complete chromatolysis. No lesions were seen in the sciatic nerves.
In occasional rats there was evidence of decreased numbers of erythrocytes and leucocytes in the peripheral blood. This occurred usually in animals that were severely intoxicated but survived for from 10 to 14 days. There was also occasional increase in the fat content of the bone marrow. However, no uniform abnormalities were seen with respect to the blood of rats.”

Any other information on results incl. tables

Table 2: mortality rates
 
Group
No. of rats
Dose level
mortality
[ml/kg bw]
[mg/kg bw]
1
10 males
0.8
ca. 690
2/10
2
10 males
1.2
ca. 1030
3/10
3
10 males
1.6
ca 1380
3/10
4
10 males
2.0
ca. 1720
4/10
5
10 males
2.4
ca. 2070
8/10
Conversion of ml into mg calculated with a density of 0.861 g/ml.

Applicant's summary and conclusion