Methodology dermal absorption study

Primary routes of entry of toxicants to the human body are dermal, gastrointestinal, and respiratory. Methods for studying these different routes are numerous, but they are perhaps best developed for the study of dermal absorption because this route is subject to more direct methodology, whereas methods for studying respiratory or gastrointestinal absorption require more highly specialized instrumentation. Additional routes encountered in experimental studies include intraperitoneal, intramuscular, and subcutaneous routes. When direct entry into the circulatory system is desired, intravenous (IV) or intra-arterial injections can be used to bypass the absorption phase. Information from this more direct route of entry (e.g., IV) should, however, be used in addition to data from the extravascular route of interest to adequately assess the true extent of absorption of a toxicant. 

In the past few years, there have been increasing efforts towards international harmonization of approaches to pesticide exposure assessment. Harmonization allows exposure assessors to share expertise and resources and develop better methods. Ongoing efforts towards international harmonization are discussed in Chapter 10. The development of generic databases has provided an impetus for harmonization of methodologies for generating the data. Further harmonization would increase the number of studies that could be included in databases, thus improving the exposure estimates derived from them. The use of harmonized factors for dermal absorption and clothing penetration, plus protective factors... 

The USEPA reviewed a number of registrant-submitted studies to assess exposure to handlers applying chlorpyrifos in agricultural and residential settings (USEPA, 2001). The biomonitoring studies measured urinary concentrations of the primary chlorpyrifos metabolite and back-calculated these to the absorbed dose of the parent. The passive dosimetry study results were corrected for 3 % dermal absorption from a human dosing study (Nolan et al 1984). The results of the studies are reported in Table 1.4 and demonstrate fairly close concordance between the two methodologies. 

Great efforts have been made to develop methods for quantitative assessments of dermal absorption. For risk assessment of chemical mixtures, many challenges are encoimtered (1) lack of quantitative data for chemical mixtures because most of the data are measured with individual chemicals (2) even for individual chemicals, only limited data acquired under comparable experimental conditions, and many data acquired imder incomparable conditions are not useful for the uigent need for risk assessment of dermal absorption (3) lack of fundamental methodology to handle thousands of chemicals and nulhons of their combinations. It is impossible to mechanistically study all of the chemicals and their combinations. This problem is likely to worsen with the increasing number of chemicals required to be evaluated. 

---