The research papers dealing with the skin absorption of a harmful gas and vapor are few and far between in view of the fact that the evaluation technique used in such research is still in its infancy. The isotopic measuring technique may be employed in such research; nevertheless it is economically prohibitive and hazardous to human life. In addition, the test solutions for the isotopic measuring technique can not be easily obtained (Hefner R E, Watanabe P G, Gehring P J. Percutaneous absorption of vinyl chloride. Toxicol. Appl. Pharmacol. 34: 529-532 (1975); Hursh J B, Clarkson T W, Goldsmith L A. Percutaneous absorption of mercury vapor by man. Arch. Environ. Health 44(2): 120-127 (1989); Corley R A, et al., Foundam. Appl. Toxicol., 39: 120-130 (1997)).
Tsuruta disclosed a method in which a mouse was anesthetized with pentabarbital and was then placed in a dynamic chamber. Immediately after being exposed to the standard gas in the dynamic chamber, the mouse was frozen by the liquid nitrogen prior to being crushed. A portion of the crushed remains of the mouse was removed and weighed. A mouse extract was obtained by a quantitative solvent. The total amount of the absorbed dose of the standard gas by the mouse was measured by gas phase chromatography (Tsuruta H. Skin absorption of organic solvent vapors in nude mice in vivo. Ind. Health 27: 37-47 (1989): Tsuruta H., et al., Ind. Health, 22: 219-212 (1984); Tsuruta H., et al., Ind. Health, 25: 215-220 (1987)). In spite of the fact that the Tsuruta's method can be carried out with precision, it can not be used to investigate the absorbed dose of the standard gas by the human body in light of tediousness and offensiveness of the method.
Currently, the most commonly used method of toxicological dynamics involves an animal or human subject, which is exposed to the standard gas in a dynamic chamber or closed exposure chamber for several hours. Thereafter, the samples are taken continuously from the subject for testing the concentration of the harmful substance or the metabolite contained in the subject's blood or tissues. The absorbed dose of the harmful substance by the subject's skin is determined by inference in conjunction with the computer model of toxicological dynamics and some hypotheses (Piotrowski J., Br. J. Ind. Med., 24: 60-65 (1967); McDougal J N., Toxicol Appl. Pharmacol., 85: 286-294 (1986)). The closed exposure chamber is defective in design in that it can not provide a stable exposure concentration, and that the control of temperature and humidity in the chamber can not be accounted for. On the other hand, the dynamic exposure chamber is capable of providing a stable exposure concentration, temperature, humidity, or wind velocity; nevertheless, it is incapable of measuring an actually absorbed dose of the gas. In addition, the dynamic exposure chamber is not cost-effective in light of a large amount of waste gas it produces. In other words, additional costly equipment is called for to deal with the waste gas. Theoretically, the absorbed dose of a substance by the skin of a subject is equal to the sum of the absorbed doses of the substance by the blood, the tissues, the organs, and the metabolite of the subject. The drawback of such a method is that the method involves a number of parameters, such as the distribution coefficients of the blood and the tissue which are derived from the data obtained from the animal experiments. In addition, the standard samples can not be easily obtained in view of the fact that the metabolites of different animals are various, and that the absorbed substance may be combined with the protein. Moreover, it is difficult to investigate the change in the absorption rate of the skin, or to know whether the absorption rate of the skin reaches saturation, during the time when the skin is exposed to the substance under investigation. This may explain the reason why there is only a limited number of articles related to the skin absorption of gas can be found (Fiber J G., et al., Arch. Toxicol., 47: 279-292 (1981); McDougal J N, Jepson G W, Clewell H J. Anderson M E. Dermal absorption of dihalomethane vapors. Toxicol. Appl. Pharmacol. 79: 150-158 (1985).; Gargas M L., Toxicol. Appl. Pharmacol., 86: 341-352 (1986)). A method for direct measurement of the absorbed dose of a substance by the animal skin has never been disclosed so far.
USPTO Backgrounds
USPTO Backgrounds