Dermal Incorporation

When organic solvents are used, the effective dermal resorption must be controlled by means of suitable protective measures. The degreasing effects of solvents increase the dermal resorption of chemicals as a consequence of damage to the skin barrier. Chemicals which can be absorbed percutaneously and which have caustic effects are incorporated extremely quickly and effectively through the skin. Fatal accidents with hydrofluoric acid and phenol are well known in the literature, the chemical incorporation being effectively increased by the caustic effect of these compounds. Lethal amounts of these substances can be incorporated within a short period of time. 

The importance of dermal incorporation in intoxication is often underestimated. Organic solvents can transport dissolved chemicals which cannot themselves be absorbed percutaneously by a kind of carrier effect In dermatology, this possibihty is often used to transport pharmaceuticals through the sldn. 

The effectiveness of dermal incorporation can be illustrated by the following example Ig (approx. 20 drops) of dimethylformamide (DMF, for formula see Fig. 2.3), a very readily skin-resorbed compound, is completely resorbed through 

For many chemicals, e.g., solvents, the following resorption times are valid  

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Studies in indoor environments of dermal contact transfer required an estimate, and a tight-fitting whole-body dosimeter was adopted and initially considered as a surrogate for skin (Krieger et al., 2000). Contact with treated surfaces was limited to feet, hands, limbs, and torso. Standardized Jazzercize to represent daily human activities and maximum contact was incorporated into protocols for indoor exposure studies (Ross et al., 1990,1991). Comparative studies will be reported elsewhere (Krieger et al., 2000). 

The bioavailability of contaminants to wildlife and humans is also an area of critical importance, where contaminants can be taken up in pore water and by dermal contact, particle ingestion, or particle inhalation. The dynamics of sorption/desorption are not currently incorporated into exposure and risk assessment models for organic compounds, where availability, in most cases, is assumed to be 100% [224]. Recently, the following have been demonstrated and reported ... 

The generally low lipid content and the poor viscosity of lipid nanodispersions make these preparations, as they are, less suitable for dermal drug application. The handling of the preparation by the patient is improved by SLN incorporation into ointments, creams, and gels. Alternatively, ready-to-use preparations may be obtained by one-step production, increasing the lipid phase to at least 30%. However, increasing the lipid frequently results in an unwanted increase in particle size. Surprisingly, it has been found that very concentrated (30 to 40%) semisolid cetyl palmitate formulations preserve the colloidal particle size [10]. 

Diethanolamine has been shown to inhibit choline uptake into cultured Syrian hamster embryo (SHE) and Chinese hamster ovary cells and to inhibit the synthesis of phosphatidylcholine in in-vitro systems in a concentration-dependent, competitive and reversible manner (Lehman-McKeeman Gamsky, 1999, 2000). Diethanolamine treatment caused a marked reduction in hepatic choline metabolite concentrations in mice following two weeks of dermal dosing. The most pronounced reduction was in the hepatic concentration of phosphocholine, the intracellular storage form of choline (Stott et al, 2000). Moreover, the pattern by which choline metabolites were altered was similar to the pattern of change that has been observed following dietary choline deprivation in rodents (Pomfret et al, 1990). Excess choline also prevented diethanolamine-induced inhibition of phosphatidylcholine synthesis and incorporation of diethanolamine into SHE cell phospholipids (Lehman-McKeeman Gamsky, 2000). 

Mathews, J.M., Gamer, C.E. Matthews, H.B. (1995) Metabolism, bioaccumulation, and incorporation of diethanolamine into phosphohpids. Chem. Res. Toxicol, 8, 625-633 Mathews, J.M., Gamer, C.E., Black, S.L. Matthews, H.B. (1997) Diethanolamine absorption, metabolism and disposition in rat and mouse following oral, intravenous and dermal administration. Xenobiotica, 27, 733-746... 

Legislation covers all chemicals, including dyes. Only the use of chemicals and colorants in foodstuffs, food-packaging materials, or pharmaceuticals is mentioned here. The exposure level of dyes is generally very low, but people are inadvertently exposed to dyes and other synthetic chemicals for these applications through dermal contact. Therefore, the use of colorants is especially regulated in many countries. General requirements on dyes for the incorporation into packa-... 

As an alternative to the assumption of a one-time exposure for 1,000 h at the time of facility closure, permanent occupancy of a disposal site following loss of institutional control could be assumed (see Section 7.1.3.4). The assumption of chronic lifetime exposure would affect the analysis for hazardous chemicals that induce deterministic effects only if estimated intakes due to additional pathways, such as consumption of contaminated vegetables or other foodstuffs produced on the site, were significant. Based on the results for lead in Table 7.8, an intake rate from additional pathways of about 50 percent of the assumed intake rate by soil ingestion, inhalation, and dermal absorption would be sufficient to increase the deterministic risk index above unity. The importance of additional pathways was not investigated in this analysis, but they clearly would warrant consideration. The increase in exposure time during permanent occupancy does not otherwise affect the analysis for chemicals that induce deterministic effects, provided RfDs are appropriate for chronic exposure, because chronic RfDs incorporate an assumption that the levels of contaminants in body organs relative to the intake rate (dose) are at steady state. 

Results Extrapolation of the results of dermal irritant/corrosivity from animals to humans is valid only to a limited degree. The findings of similar test results in other animal species may give more weight to extrapolation of animal studies to humans. The results of the experiment may be presented in a tabular form incorporating all the aspects of the study, and as with acute oral toxicity. 

Riviere JE, Brooks JD. 2007. Prediction of dermal absorption from complex chemical mixtures incorporation of vehicle effects and interactions into a QSPR framework. SAR QSAR Environ Res 18 31 -4. 

The SCIES and MCCEM models give only inhalation exposure, but the simulated results can be incorporated into a whole-risk assessment in the residential space such as the USEPA SOP framework (USEPA, 1997b) which estimates multiple exposure levels via all routes (i.e. inhalation, dermal and oral). THERdbASE is capable of estimating inhalation and dermal exposures based on the simulated airborne concentration and the film-thickness theory, and InPest estimates all exposures, including oral routes, based on the simulated concentration in the air and amounts on the room materials (Matoba et al., 1998c). 

Probabilistic risk assessment methods are used to incorporate uncertainty and variability into both aggregate and cumulative risk assessments. Herein, uncertainty refers to lack of knowledge or the limitations in the current state of knowledge. For example, the dermal permeability of a pesticide may not be known with certainty. Variability, on the other hand, refers to a value that differs from one individual to another individual in a population or from one instance to another. For example, the number of apphcations of a residential pesticide in a year may vary from one individual to another. Probabilistic methods use probability distributions to incorporate uncertainty and variability into both aggregate and cumulative risk assessments. 

Haugh JM. Deterministic model of dermal wound invasion incorporating receptor-mediated signal transduction and spatial gradient sensing. Biophys. J. 2006 90 2297-2308. 

KIO. Kowalewski, K., Incorporation of radiosulfur into the dermal connective tissue of hypothyroid rat. Acta Endocrinol. 28, 124-128 (1958). 

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