UDC 613.632:678.044.46

N. I. Shumskaya, V. V. Melnikova, Yu. G. Chikishev, E. P. Taraday

On the Toxicity of Extracts from Rubbers Made with Different Rubber Bases and Containing Thiuram in Their Formulations

Research Institute of Rubber and Latex Products, Moscow

The widespread use of rubber products in the food industry and medicine has made it necessary to assess their hygienic and sanitary-chemical properties. Studies in recent years have established that, during use, rubbers can release individual ingredients into the media with which they come into contact (N. F. Kazarinova et al.; L. N. Bidnenko and N. Yu. Grushevskaya; V. V. Stankevich and E. A. Shurupova), adversely affecting the body. Thiuram is the vulcanization accelerator most commonly used in rubber manufacture. Although the toxicity of thiuram itself has been studied extensively, there is still no single, unequivocal criterion for the hygienic assessment of rubbers containing it and made with different rubber bases. It was therefore of interest to compare the toxicity of rubber extracts with the migration of thiuram and its possible transformation products as a function of the rubber formulation—specifically, the rubber base and filler. Extracts from four rubber samples were studied.

The rubber samples differed in the type of rubber and filler and contained the same amount of accelerator. Two rubber grades (IR-34A and IR-34P) were made from smoked-sheet natural rubber, while the other two (IR-34L and IR-34N) were made from SKN-26 synthetic rubber. The IR-34A and IR-34L rubbers contained a carbon black filler (DG-100 and TGM-33 carbon black) in equal volumes, while the others contained a light-colored filler, chalk. The remaining ingredients (zinc oxide, mineral oil, stearin, and sulfur) were identical in both kind and quantity in the four rubber grades studied.

Aqueous rubber extracts were prepared by steeping the rubber in distilled water at a total surface-area-to-liquid-volume ratio of 1:2 for 24 hours at room temperature, in accordance with the Instructions for the Sanitary-Chemical Examination of Rubbers and Products Made from Them Intended for Contact with Foodstuffs, No. 1400a-75. Thiuram and cimate, a transformation product of thiuram, were determined in the prepared extracts by thin-layer chromatography.

Thiuram and cimate were separated in a thin layer of silica gel on Silufol plates (Czechoslovakia) by two successive chromatographic runs using methylene chloride as the mobile phase. A modified ninhydrin reagent was used as the color reagent. The compounds of interest appeared as greenish-brown spots, with \(R_f\) values of \(0.56 \pm 0.04\) for cimate and \(0.32 \pm 0.04\) for thiuram and detection sensitivities of 1 and 0.5 µg, respectively. In addition to thiuram and cimate, carbon disulfide (M. V. Alekseeva et al.) and methacrylic acid (A. A. Russkikh) were determined in the extracts, as were the aggregate indicators of oxidizability (permanganate oxidizability and bromine-reactive compounds).

The data obtained indicate that thiuram and cimate migrate into aqueous extracts from all the rubbers studied, with a combined concentration of approximately 1.0 mg/L. Neither the type of rubber nor the type of filler affected the extent of migration of these substances.

The toxicity of the rubber extracts was assessed in a three-month experiment on male albino rats with initial body weights of 180–190 g. The test animals were given aqueous extracts daily by gastric administration at a dose of 20 mL/kg; the controls received the same volume of distilled water. Extract toxicity was assessed using a set of indicators characterizing the animals’ general condition and individual organs and systems: body weight, threshold of neuromuscular excitation, functional state of the liver and kidneys, and peripheral blood composition. These indicators were examined monthly. At the end of the experiment, all animals were killed. Total serum protein, organ-to-body-weight ratios, and pathological changes in the organs were determined.

The studies showed that the test animals gained weight at the same rate as the controls. No abnormalities in the nervous system were detected in the test animals compared with the controls. Hemoglobin, leukocyte, and erythrocyte levels in the blood of the test rats remained normal, but animals receiving extracts from rubbers based on SKN-26 synthetic rubber (grades IR-34L and IR-34N) showed changes in kidney and liver function and in organ-to-body-weight ratios. One month after the start of the experiment, the test animals showed a sustained increase in urinary protein and a decrease in urinary chloride concentration, as well as a difference in hippuric acid content compared with the controls. A significant decrease in kidney-to-body-weight ratios was observed in animals receiving extracts from both SKN-26-based rubber samples, and a decrease in the heart-to-body-weight ratio was observed in animals receiving the IR-34N rubber extract.

Notably, extracts from natural-rubber-based materials were considerably less toxic than those from SKN-26-based rubbers. The extract from the IR-34A rubber compound caused only a transient change in urinary protein levels,

...which did not exceed the physiological range of variation for this parameter in control rats, as well as a change in the kidney weight coefficient.

In animals given extracts from IR-34P rubber, none of the intoxication parameters studied differed from those in the control groups.

Conclusions

1. The same degree of migration of thiuram and zimate (approximately 1 mg/L in total) from the rubbers was observed regardless of the rubber base and filler (natural rubber and SKN-26; chalk and carbon black).
2. Extracts from SKN-26-based rubbers are more toxic than extracts from natural-rubber-based rubbers at equal concentrations of thiuram and zimate.

References

Alekseeva, M. V., Andronov, B. E., and Gurvich, S. S. Determination of Harmful Substances in the Air of Industrial Premises. Moscow, 1954, p. 404.

Bidnenko, L. N., and Grushevskaya, N. Yu. Gigiena i sanitariya, 1974, no. 11, pp. 28–30.

Kazarinova, N. F., Grushevskaya, N. B., and Shurupova, E. A. Voprosy pitaniya, 1974, no. 4, pp. 64–68.

Russkikh, A. A. Zavodskaya laboratoriya, 1973, no. 15, p. 4.

Stankevich, V. V., and Shurupova, E. A. Gigiena i sanitariya, 1976, no. 9, pp. 24–26.

Received February 10, 1978.