Musk xylene: analysis, occurrence, kinetics, and toxicology.

1,3-Dimethyl-2,4,6-trinitro-5-tert.-butylbenzene (musk xylene, MX), a synthetic musk, is often used in fragrances and soaps to substitute the natural musk. MX belongs to the common group of nitromusk compounds. The main environmental intake of MX occurs after sewage introduction. The consumption of fish and drinking water as well as the use of body care and perfumed household products could lead to an ingestion of this substance in humans. Although the acute oral and dermal toxicity of MX is low, some hint for the carcinogenic potential of MX was found in one animal experiment. These findings and the high potential of MX as environmental contaminant, it is stable against biological and chemical degradation and it is highly lipophil, raised considerable attention in the field of environmental medicine. Biological monitoring and the toxicology of MX, which previously has been described to occur in human milk, human fat tissue, as well as human blood samples, are of central interest. The aim of this article is to summarize the data on the analysis, occurrence, kinetics, and toxicology of MX. As there is a lack of knowledge on human toxicity and human carcinogenicity of MX, a final evaluation of the toxicological data with regard to public health is still impossible. Nevertheless, in view of the published data about MX, there is no evidence for any substantial human risk at the moment.

The rate of percutaneous permeation of xylene, measured using the "perfused pig ear" model, is dependent on the effective protein concentration in the perfusing medium.

In order to study the dermal permeation of compounds through the skin, an in vitro model was developed which utilized pig ears perfused with autologous pig blood (de Lange, J., van Eck, P., Elliott, G. R., de Kort, W. L. A. M., and Wolthuis, O. L. (1992). J. Pharmacol. Toxicol. Methods 27, 71-77). In the present article we investigated to what extent the rate of permeation of xylene through pig ear skin is dependent on the perfusion medium used. Pig ears were exposed to xylene (10 cm2 area) for a 4-hr period (30 degrees C, relative humidity of 40-60%) and the perfusate was analyzed for xylene using gas chromatography. The rates of permeation of xylene for whole blood, blood depleted of white blood cells, and a buffer containing 4.5% albumin were similar (+/- 300 ng/min/cm2). The rate of penetration was fivefold higher when pig plasma was used and ninefold lower when albumin was excluded from the buffer. Using the buffer, we found that the rate of permeation of xylene was proportional to flow (constant protein concentration) and protein concentration (constant flow). Our data demonstrate that the measured permeation rate for xylene is, to a large degree, dependent on the effective protein concentration (mg/min) passing through the ear. Differences in this parameter could explain the variations in rates of permeation found using the different perfusion media. To avoid problems associated with the choice of receptor fluid for permeation experiments, we suggest that full blood remains the vehicle of choice, although the practical perfusion period is limited to about 6 hr. If longer perfusion periods are required, then it should be possible to reproduce results obtained with whole blood by choosing an appropriate buffer.