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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract

Data source

Reference
Reference Type:
publication
Title:
The toxicology of vinylcyclohexane
Author:
Savchenkov M.F.
Year:
1965
Bibliographic source:
Gigiena i Sanitariya 30 Vol. 7, 32-37

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
Vinylcyclohexane
EC Number:
211-779-3
EC Name:
Vinylcyclohexane
Cas Number:
695-12-5
Molecular formula:
C8H14
IUPAC Name:
vinylcyclohexane

Administration / exposure

Route of administration:
inhalation: vapour
Vehicle:
air
Duration of treatment / exposure:
4 hours per day for 3.5 months
Frequency of treatment:
daily
Doses / concentrations
Dose / conc.:
0.42 mg/L air (nominal)
Remarks:
0.2-0.6 mg/L with an average of 0.42 mg/L

Results and discussion

Effect levels

Dose descriptor:
LOAEC
Effect level:
0.42 mg/L air (nominal)
Based on:
test mat.
Sex:
not specified
Remarks on result:
other: see Remarks
Remarks:
They caused disturbances in several of the animals functions, mainly in the central nervous and cardiovascular systems. Histological investigations revealed considerable dystrophic changes in the cells of the liver and kidney parenchyma, hypertrophy of the medullary cells and atrophy of the cortical cells of the suprarenals. Some experimental animals (2 rats) died by the end of the exposure period. The dead animals had gross degenerative changes in the liver and especially in the kidneys.

Any other information on results incl. tables

In long-term inhalation experiments, VCH concentrations varying from 0.2 -0.6 mg/L, an average of 0.42 mg/L were used. Rabbits and albino rats were exposed to low concentrations of VCH vapour for 4 hours daily over a period of 3.5 months. During the long-term experiments, fortnightly examinations were made of the nervous and cardiovascular systems, the morphological composition of the blood, the functional state of the liver, and the oxygen consumption. Similar examinations had been performed prior to the experiment. At the end of the treatment period, some of the rats were killed, and their organs were examined histologically. The remaining animals were used for study the recovery period. The functional state of the CNS was assessed from the length of the animals hypnosis and from changes in the characteristics of the flexion reflex.

The results obtained by both methods were in agreement. A certain disequilibrium and excitability of the CNS of the animals which was noted at the beginning of the period of inhalation was subsequently replaced by the development of inhibitory processes. Some animals developed equalizing and paradoxical phases. The marked inhibition of the rabbits could also be shown by the length of the animals hypnosis. The difference between the length of hypnosis in the experimental and the control rabbits was especially marked during the 3rd month of exposure.

There were no notable changes in the blood picture during the first two months of exposure. In the third month, there was some inhibition of hemopoiesis as expressed by a decrease in the absolute number of erythrocytes and leukocytes. There was a decrease in the immunobiological state of the animals after three weeks of exposure. The phagocytic activity (number) and phagocytosis intensity (phagocytic index) of leukocytes decreased appreciably in comparison to the initial level. However, after a further week, the phagocytic number and phagocytic index began to increase and approach the initial level. Two weeks later they exceeded the initial level and this was followed by another, still more marked decrease in phagocytic activity and intensity of phagocytosis. By the end of the period of exposure the phagocytic number in the experimental rabbits was 43% as compared with a mean of 56% in the control animals. The phagocytic index was 4.7 as compared with 7.8 in the control rabbits.

The most distinct index was provided by variations of the blood pressure of albino rats, which was measured with Kogans experiment. The blood pressure began to decline 15 days after the beginning of exposure. The decrease was similar in males and females during the first two months, but subsequently became more pronounced in the females. The decline of blood pressure was more pronounced in rats exposed to VCH vapour in the second half of the period.

The functional state of the liver was examined by means of the Quick-Pytel and hexenal tests which revealed some inhibition of the detoxicating function. This was demonstrated best by the hexenal test. The narcosis time in the experimental rats was 18 -20 min as against 10 -12 min in the control animals. The oxygen consumption was also studied and showed that there was a considerable difference in the second half of the exposure period. A very characteristic feature was the decrease in the body temperature of the experimental rats.

In animals killed after the termination of the chronic experiments it was found that there was an increased weight coefficient of the lungs, kidneys and spleen and especially of the suprarenals and thyroid.

Microscopy revealed hyperemia of the myocardium and lungs, hyperemia and dystrophic changes in the liver parenchyma cells, stimulation of the spleen and stagnant hyperemia, hemorrhagic foci and degenerative changes in the tubular epithelium in the kidneys. The suprarenals showed hyperemia and hypertrophy of the medullary cells and atrophy of the cortical cells.

Examinations performed during the recovery period showed that all the disturbances were reversible. One and a half months after the termination of the exposure period all the animals’ functions returned to normal.

The working capacity of the experimental and control animals in the recovery period was tested on a treadmill. The working capacity of the control animals was considerably greater than that of the experimental animals although the latter had recovered all their normal functions. When the working capacity test was repeated two weeks later, there was no differences anymore.

The concentration used in the chronic experiment proved to be effective. They caused disturbances in several of the animal's functions, mainly in the central nervous and cardiovascular systems. Histological investigations revealed considerable dystrophic changes in the cells of the liver and kidney parenchyma, hypertrophy of the medullary cells and atrophy of the cortical cells of the suprarenals. Some experimental animals (2 rats) died by the end of the exposure period. The dead animals had gross degenerative changes in the liver and especially in the kidneys.

Applicant's summary and conclusion

Conclusions:
The concentration used in the chronic experiment (mean 0.42 mg/L) caused disturbances in several of the animals functions, mainly in the central nervous and cardiovascular systems.
Executive summary:

In long-term inhalation experiments. rabbits and albino rats were exposed to 0.2-0.6 mg/L of VCH vapour for 4 hours daily over a period of 3.5 months. Fortnightly examinations were made of the nervous and cardiovascular systems, the morphological composition of the blood, the functional state of the liver, and the oxygen consumption. At the end of the poisoning period, some of the rats were killed, and their organs were examined histologically. The remaining animals were used for study the recovery period. The functional state of the CNS was assessed from the length of the animals hypnosis and from changes in the characteristics of the flexion reflex.

The functional state of the liver was examined by means of the Qucik-Pytel and hexenal tests which revealed some inhibition of the detoxicating function. The narcosis time in the experimental rats was 18 -20 min as against 10 -12 min in the control animals. In animals killed after the termination of the chronic experiments it was found that there was an increased weight coefficient of the lungs, kidneys and spleen and especially of the suprarenals and thyroid. Microscopy revealed hyperemia of the myocardium and lungs, hyperemia and dystrophic changes in the liver parenchyma cells, stimulation of the spleen and stagnant hyperemia, hemorrhagic foci and degenerative changes in the tubular epithelium in the kidneys. The suprarenals showed hyperemia and hypertrophy of the medullary cells and atrophy of the cortical cells. Examinations performed during the recovery period showed that all the disturbances were reversible. One and a half months after the termination of the exposure period all the animals’ functions returned to normal.

The concentration used in the chronic experiment proved to be effective. They caused disturbances in several of the animals functions, mainly in the central nervous and cardiovascular systems. Histological investigations revealed considerable dystrophic changes in the cells of the liver and kidney parenchyma, hypertrophy of the medullary cells and atrophy of the cortical cells of the suprarenals. Some experimental animals (2 rats) died by the end of the exposure period. The dead animals had gross degenerative changes in the liver and especially in the kidneys.