4-tert-butyltoluene

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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:

The study was carried out according to the following references:
- Hine CH et al (1953). Toxicology and Safe Handling of CBP-55 (Technical 1-Chloro-3-Bromopropene-1). AMA Arch Ind Hyg 7: 118-136.
- Draize J et al (1944). Methods for the Study of Irritation and Toxicity of Substances Applied Topically to the Skin and Mucous Membranes. J Pharm Exp Ther 82: 377-390.

GLP compliance:

no

Remarks:

pre-GLP study

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

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:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no further data on animals and environmental conditions

Administration / exposure

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

No further details given.

Duration of exposure:

no further data

Doses:

ca. 9210, 13350, 19630 mg/kg bw (Original value: up to 10.7, 15.5, 22.8 ml/kg bw)

No. of animals per sex per dose:

totally 20 animals; see freetext

Control animals:

no

Details on study design:

- Duration of observation period following administration: 10 or 14 days; not exactly defined
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs for all animals. RBC, WBC, Hb, gross pathology and histopathology of decedents.
The rabbits were removed from the holder after 24 hours and examined for local and general effects. Moribund animals were killed for necropsy; blood was drawn for red and white cell counts and hemoglobin estimation, and suitable tissues were taken for histologic examination.

Statistics:

LD50 was calculated by the method of Thompson WR (1947). Use of Moving Averages and Interpolation to Estimate Median-Effective dose. Bact Rev 11: 115-145.

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 16 880 mg/kg bw

95% CL:

11 880 - 23 940

Remarks on result:

other: Original value: LD50 = 19.6 (13.8 - 27.8) ml/kg bw; density: 0.861 g/ml

Mortality:

None of totally 12 rabbits given up to 10.7 ml/kg bw died. Five of totally 8 animals given 15.5 or 22.8 ml/kg bw died.
No further data.

Clinical signs:

other: None of the 12 rabbits receiving up to 10.7 ml/kg bw showed evidence of intoxication, but at 15.5 and 22.8 ml/kg bw, five of totally eight animals showed evidence of severe alterations in physiology and subsequently died. The survivors showed only minima

Gross pathology:

The results of gross pathology are described in a generalized manner.
Gross changes included marked liver damage and some evidence of irritation of the pulmonary tract. 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, and enlargement and marked yellowish discoloration of the liver.

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."