Attenuated-total-ref lectance Fourier-transform-infrared spectroscopy has been used to rapidly and noninvasively quantify in vivo the uptake of a chemical into the outermost, and least permeable, layer of human skin (the stratum corneum). The objective of the experiment was to develop a general model to predict the rate and extent of chemical absorption for diverse exposure scenarios from simple, and safe, short-duration studies. Measurement of the concentration profile of the chemical in the stratum corneum, and analysis of the data using the unsteady-state diffusion equation, enabled estimation of the permeability coefficient and calculation of the time required to achieve maximal transdermal f lux. Validation of the spectroscopic technique employed was established, and quantitation of chemical uptake into the stratum corneum was confirmed independently using trace amounts of radiolabeled chemical in conjunction with liquid scintillation counting and accelerator mass spectrometry. The results presented have pharmacological and toxicological implications, as the technology lends itself both to the prediction of transdermal drug delivery, and the feasibility of this route of administration, and to the assessment of risk after dermal contact with toxic chemicals.The principal function of the skin is to act as a barrier to the insensible loss of tissue water. This objective is achieved by the stratum corneum (SC), the outermost layer of the epidermis, a lipid-protein biphasic structure, having a thickness of only 10 -20 m on most surfaces of the body. The excellent diffusional resistance of the SC makes the transdermal delivery of drugs at best difficult and frequently impossible. On the other hand, the SC protects against the dermal exposure of the organism to toxic chemicals. Nevertheless, there remains an important pharmaceutical need to reliably predict the topical and/or transdermal bioavailability of cutaneously applied drugs, and there is a crucial regulatory requirement for the accurate estimation of risk when inadvertent contact occurs between a potentially harmful substance and the skin.Because of the transport rate-limiting ability of the SC, it is reasonable to suppose that, from a chemical's concentration profile across the membrane, even after a relatively short exposure, all necessary information relating to permeability can be deduced. In this regard, previous research has involved application of radiolabeled chemicals followed by SC removal using repeated adhesive tape-stripping, and analysis of the tape-strips by liquid scintillation counting (1). If the dose is sufficiently large, on the other hand, and a suitable extraction procedure is available for the chemical, more conventional analytical tools (e.g., HPLC) can be used. While these approaches have been used in humans, neither is particularly satisfying because of the need to expose the subjects to a significant amount of radioactivity or to a possibly excessive quantity of the chemical itself.Recently, attenuated-total-reflectance F...

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Heterocyclic amines ( HAs ) formed in fried, broiled or grilled meats are potent mutagens that increase rates of colon, mammary, prostate and other cancers in bioassay rodents. Studies of how human dietary HA exposures may affect cancer risks have so far relied on fairly crudely defined HA -exposure categories. Recently, an integrated, quantitative approach to HA -exposure assessment ( HAEA ) was developed to estimate compound -specific intakes for particular individuals based on corresponding HA -concentration estimates that reflect their meat -type, intake -rate, cooking -method and meat -doneness preferences. This method was applied in the present study to U.S. national Continuing Survey of Food Intakes by Individuals ( CSFII ) data on meats consumed and cooking methods used by > 25,000 people, after adjusting for underreported energy intake and conditional on meat -doneness preferences estimated from additional survey data. The U.S. population average lifetime time -weighted average of total HAs consumed was estimated to be $9 ng / kg / day, with 2 -amino -1 -methyl -6 -phenylimidazo [ 4,5 -b ] pyridine ( PhIP ) estimated to comprise about two thirds of this intake. Pan -fried meats were the largest source of HA in the diet and chicken the largest source of HAs among different meat types. Estimated total HA intakes by male vs. female children were generally similar, with those by ( 0 -to 15 -year -old ) children $25% greater than those by ( 16 + -year -old ) adults. Race -, age -and sex -specific mean HA intakes were estimated to be greatest for African American males, who were estimated to consume $2 -and $3 -fold more PhIP than white males at ages < 16 and 30 + years, respectively, after considering a relatively greater preference for more well -done items among African Americans based on national survey data. This difference in PhIP intakes may at least partly explain why prostate cancer ( PC ) kills $2 -fold more African American than white men, in view of experimental data indicating that PhIP mutates prostate DNA and causes prostate tumors in rats. Journal of Exposure Analysis and Environmental Epidemiology ( 2001 ) 11, 155 ± 168.

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