Dermal uptake

Sex differences in uptake and metabolism of trichloroethylene have been seen in both humans and animals (see Section 2.8). Studies with male and female rats given various levels of testosterone have implicated this hormone in determining the degree of dermal penetration of trichloroethylene (McCormick and Abdel-Rahman 1991). The mechanism behind this effect is still unclear. 

Absorbed Dose, Chemical—The amount of a substance that is either absorbed into the body or placed in contact with the skin. For oral or inhalation routes, this is normally the product of the intake quantity and the uptake fraction divided by the body weight and, if appropriate, the time, expressed as mg/kg for a single intake or mg/kg/day for multiple intakes. For dermal exposure, this is the amount of material applied to the skin, and is normally divided by the body mass and expressed as mg/kg. 

Some dermal uptake of diisopropyl methylphosphonate through the skin of rabbits can be inferred based on the death of 3 of 4 animals treated with 2,000 mg/kg neat applied to shaved abraded or unabraded skin for a 24-hour period (Hart 1976). 

In addition, the use of biological monitoring has the advantage that skin penetration under particular conditions of protective clothing is included as well in the approach. The results of a dose-excretion study of propoxur by Meuling et al. (1991) using volunteers indicate a significant increase of the dermal uptake of the compound under conditions of occlusion, where there is increased blood flow, skin temperature, and skin moisture. 

Figure 2.5 A broken, spherical silica particle entrapping an API has 85% free volume. Such particles are used in formulations such as Eusolex UV-Pearls that reduce dermal uptake compared to free UV filters thus they do not irritate the skin while they make new application possibilities for hydrophobic UV filters. (Photo courtesy of Sol-Gel Technologies Ltd.)... 

Comparative studies on the bioavailability of three different tretinoin gel formulations showed that the dimensions of the sampling area may play a critical role in determining the extent of dermal drug uptake [33, 34], If, by lateral spreading, a substance is distributed over an area sufficiently larger than the sampling area, significant proportions of compound will not be recovered and hence permeability will be underestimated. 

These studies show that when the accumulation of HOCs occurs solely by respiration or dermal absorption, BMO and SPMD rate constants correlated very well, but that concentrations in SPMDs are often higher than those in BMOs. However, good correlations between the fingerprints or patterns of HOC residues in BMO tissues and SPMDs would not be expected to hold, when diet plays a major role in the uptake of compounds with high TfowS (see Eq. 7.5). For example, Peven et al. (1996) compared the accumulation of organic contaminants by transplanted... 

A dermal absorption rate of 329 mnol/minute/cm ( 60 nmol/minute/cm ) was calculated for the shaved abdominal skin of mice (Tsumta 1975). This is equivalent to a human absorption rate of 29.7 mg/minute, assuming that a pair of hands are immersed in liquid chloroform (Tsumta 1975). However, this calculation was based on the assumptions that the rate of chloroform penetration is uniform for all kinds of skin and that the total surface area of a pair of human hands is 800 cm the former assumption is especially dubious. Islam et al. (1995) investigated the fate of topically applied chloroform in male hairless rats. For exposures under 4 minutes, chloroform-laden water was applied to shaved back skin for exposures of 4-30 minutes, rats were submerged in baths containing chloroform-laden water. Selected skin areas were tape-stripped a various number of times after various delay periods. It appeared that there was an incremental build-up of chloroform in the skin over the first four minutes. When compared to uptake measured by bath concentration differences, approximately 88% of lost chloroform was not accounted for in the stratum comeum and was assumed to be systemically absorbed. 

Description of the Model. The McKone (1993) PBPK model addressed potential exposure to chloroform by the inhalation and dermal routes. McKone revised existing shower-compartment, dermal uptake and PBPK models to produce a revised PBPK model for simulating chloroform breath levels in persons exposed in showers by the inhalation route only and by the inhalation and dermal routes combined. Parameters used by this model were taken primarily from two main sources, Jo et al. (1990a) and Corley et al. (1990). 

Xu X, Weisel CP (2005) Dermal uptake of chloroform and haloketones during bathing. J Exp Anal Environ Epidemiol 15(4) 289-296... 

Kafferlein HU, Angerer J (2001) Trends in the musk xylene concentrations in plasma samples from the general population from 1992/1993 to 1998 and the relevance of dermal uptake. Intern Arch Occup Environ Health 74 470-476... 

Molecular weight Less than 100 favors dermal uptake. Above 500 the molecule may be too large. 

Water solubility The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore, if the water solubility is below 1 mg/1, dermal uptake is likely to be low. Between 1 and 100 mg/1 absorption is anticipated to be low to moderate and between 100 and 10,000 mg/1 moderate to high. However, if water solubility is above 10,000 mg/1 and the Log P value below 0, the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum and dermal uptake for these substances will be low. 

An exposure assessment is the quantitative or qualitative evaluation of the amount of a substance that humans come into contact with and includes consideration of the intensity, frequency and duration of contact, the route of exposure (e.g., dermal, oral, or respiratory), rates (chemical intake or uptake rates), the resulting amount that actually crosses the boundary (a dose), and the amount absorbed (internal dose). Depending on the purpose of an exposure assessment, the numerical output may be an estimate of the intensity, rate, duration, and frequency of contact exposure or dose (the resulting amount that actually crosses the boundary). For risk assessments of chemical substances based on dose-response relationships, the output usually includes an estimate of dose (WHO/IPCS 1999). 

For a better idea of the toxicity of VOCs, we can look more closely at some studies of TCE (Bogen et al., 1998). In vitro uptake of C-14-labeled trichloroethylene (TCE) from dilute (similar to 5-ppb) aqueous solutions into human surgical skirt was measured using accelerator mass spectrometry (AMS). The AMS data obtained positively correlate with (p approximate to 0) and vary significantly nonlinearly with (p = 0.0094) exposure duration. These data are inconsistent (p approximate to 0) with predictions made for TCE by a proposed EPA dermal exposure model, even when uncertainties in its recommended parameter values for TCE are considered but are consistent (p = 0.17) with a 1-compartment model for exposed skin-surface. This study illustrates the power of AMS to facilitate analyses of contaminant biodistribution and uptake kinetics at very low environmental concentrations. Eurther studies could correlate this with toxicity. 

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). 

Methods for Determining Parent Compounds and Degradation Products in Environmental Media. Human exposure to diazinon occurs via inhalation of ambient air ingestion of contaminated food and water and dermal uptake through occupational and non-occupational contact with contaminated soils, surface water, and commercial preparations. Methods have been reported for the measurement of... 

APase in onion roots. Enzyme activity was mainly extracellular with the heaviest concentration in corner spaces between the epidermal and hypo-dermal layers. He suggested the possibility of a subcutaneous pore through which the enzyme could be released to the root surface. Bieleski and co-workers (Reid Bieleski, 1970 Bieleski Johnson, 1972) studied the psi induction and location of APase in duckweed (Spirodela oligorrhiza). APase in control plants was located primarily in and around the vascular strands. In P-deficient plants psi-APase activity was 10-20 times the control value. Enzyme activity was primarily located in the epidermis of the root and undersurface of the frond, the tissue locations most likely to provide access to phosphate esters in the medium. These workers further demonstrated that hydrolysis of organic phosphates occurred in the external medium and/or the apoplast followed by Pi uptake into the cell. 

Dermal. Dermal administration is required for estimation of toxicity of chemicals that may be absorbed through the skin, as well as for estimation of skin irritation and photosensitization. Compounds are applied, either directly or in a suitable solvent, to the skin of experimental animals after hair has been removed by clipping. Often dry materials are mixed with water to make a thick paste that can be applied in a manner that ensures adequate contact with the skin. Frequently the animals must be restrained to prevent licking and hence oral uptake of the material. Solvent and restraint controls should be considered when stress is involved. Skin irritancy tests may be conducted on either animals or humans, using volunteer test panels for human tests. 

This is the process by which the chemical concentration in an aquatic organism achieves a level that exceeds that in the water, as a result of chemical uptake through all possible routes of chemical exposure (e.g., dietary absorption, transport across the respiratory surface, dermal absorption, inhalation). 

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