INTRODUCTION There is increasing concern over the skin as a route of entry into the body for toxic substances@ particularly in the work environment where the number of potentially harmful substances is large and exposure may be of long duration. Whereas the skin had previously been thought to be a relatively impervious barrier@ more recent work has clearly shown that it is a barrier of variable permeability. Some substances are indeed excluded from entry into the body by the skin@ but most are not. Indeed@ it has been shown that the skin is very permeable to simple compounds such as benzoic acid and dinitrochlorobenzene@ with approximately 50% of an applied dose being absorbed in twenty-four hours. Thus@ a critical factor In the evaluation of the risk associated with cutaneous exposure to toxic substances Is information relating to the percutaneous absorption of those substances. During the past few years this laboratory has begun a systematic investigation of the percutaneous absorption of a number of petroleum derived chemicals: benzene@ toluene@ xylene@ naphthalene and benzo(a)pyrene. As a starting point two animal models were utilized@ the monkey and miniature pig@ and both in vitro and in vivo studies were conducted. In the first year work focused largely on a comparison of the models@ monkey versus mini-pig and In vitro versus In vivo. In both cases it was found that the data obtained were essentially equivalent. Absorption appeared to be independent of the species or methodology used. During the second year the studies were extended to man and@ because of the greater concern for its toxicity@ focused almost entirely on benzene. In the third year of the project work continued to focus largely on benzene and three specific areas were examined: 1) absorption as a function of time of exposure@ 2) absorption from a gasoline vehicle@ and 3) absorption from the vapor phase.In addition@ during the third year studies were initiated on the absorption of a new petroleum derived chemical - isooctane. Special problems were encountered in the measurement of isooctane absorption and progress in this phase of the project was limited. In the present contract year@ year 4@ the focus has been almost exclusively on isooctane and this report will discuss the results obtained both in vitro (human) and in vivo (monkey). Data obtained from the final phase of the benzene work@ vapor phase absorption@ wi 11 also be presented; and finally@ limited in vivo studies on toluene absorption through human palmar skin will be presented.
API PUBL 37-31827-1987 history
1987API PUBL 37-31827-1987 Absorption of Petroleum Products Across the Skin of Monkey and Man Final Report