Surface area of skin

SKIN This designation sometimes appears alongside a TLV or PEL. It refers to the possibility of absorption of the particular chemical through the skin and eyes. Thus, protection of large surface areas of skin should be considered to prevent skin absorption so that the TLV is not invalidated. 

The transcellular pathway has been discredited as a major pathway, although some polar substances can penetrate the outer surface of the protein filaments of hydrated stratum comeum. The transfollicularpathway is really an invagination of the epidermis into the dermis, and the chemical still has to penetrate the epidermis to be absorbed into the blood stream. This is also a regarded as minor route. Sweat pores are not lined with the stratum comeum layer, but the holes are small, and this route is still considered a minor route for chemical absorption. In general, the epidermal surface is 100 to 1000 times the surface area of skin appendages, and it is likely that only very small and/or polar molecules penetrate the skin via these appendages. 

TABLE 2-7 Surface Area of Skin Normally Exposed in Humans After Casual Work Dress... 

Virtually all man-made chemicals have the potential to contact the skin of people. In fact, many (e.g., cosmetics and shampoos) are intended to have skin contact. Also, the most common medical problems in industrial workers are skin conditions, reflecting the large extent of dermal exposure where none is intended. When a large surface area of skin is exposed to contaminated soil or water, skin absorption may be significant. It is also possible for dermal effects to arise from systemic toxicants. 

The severity of poisoning due to skin contact depends on the surface area of skin exposed applying an 80% MCA solution on less than 5% of the body surface area can cause severe poisoning, while exposing 6-10% of the body surface to MCA is often lethal. 

Chemicals have to pass through either the skin or mucous membranes lining the respiratory airways and gastrointestinal tract to enter the circulation and reach their site of action. This process is called absorption. Different mechanisms of entry into the body also greatly affect the absorption of a compound. Passive diffusion is the most important transfer mechanism. According to Pick s law, diffusion velocity v depends on the diffusion constant (D), the surface area of the membrane (A), concentration difference across the membrane (Ac), and thickness of the membrane (L)... 

Metabolic rate class Related to a unit skin surface area (W m-2) Total (for a mean skin surface area of 1.8 m") (W) Person acclimatized to heat (°C) Person not acclimatized to heat (°C) ... 

In rats in which a 0.03-mg/kg dose of [14C]-labeled phenol was placed on the skin, only 1-5% of the dose remained in the body 72 hours later (Hughes and Hall 1995). The dermal absorption of phenol was studied in three pigs in which undiluted phenol was placed on the skin for 1 minute, and the peak plasma level was determined (Pullin et al. 1978). Plasma levels were not measurable in 1 pig treated with a dose of 90 mg/kg over a surface area of 91.6 cm2. In pigs treated with a dose of 500 mg/kg, peak plasma levels of 0.9 and 30.5 ppm were reported in pigs treated over surface areas of 91.6 and 1,135.5 cm2, respectively. 

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. 

To pass into the skin, the substance must enter through one or more of the following routes the epidermal cells, the sweat glands, the sebaceous glands, or the hair follicles. The pathway through the stratum corneum and the epidermal cells is the main avenue of penetration, as this tissue constitutes the majority of the surface area of the skin. 

Exposure of rats to 800 ppm for 15 minutes was fatal, but nearly all survived when exposed for 13 minutes. There was severe inflammation of all exposed mucosal surfaces, resulting in lacrimation, corneal ulceration, and burning of exposed areas of skin. In another study, exposure of rats to 480 ppm for 40 minutes or to 96ppm for 3.7 hours was fatal in the latter group, effects were pulmonary edema and marked irritation of the bronchial mucosa. Chronic exposure of dogs and rats to about Ippm, 6 hours/day for up to 6 months caused severe pulmonary irritation and some deaths. ... 

Respiration into the lung alveoli is the most important hazard for plant workers. The average lung has 300 million alveoli with a surface area of about 70 m, which is designed for rapid gas exchange. This alveolar surface area is about 40 times larger than the external skin area of a person. There has been a systematic study of the major air pollutants associated with the protection of industrial workers, as monitored by the OSHA and the ACGIH, and there are three well-documented measurements and databases ... 

The other major route of chemical hazards to plant workers is penetration through the skin, which has a surface area of about 1.8 m for a male adult, and is lined with a tough horny layer of densely packed cells without nuclei. So the skin is reasonably impervious to the penetration of chemical substances, and penetration depends on the lipid solubility of the compound, where the diffusion speed is inversely related to molecular weight. Skin penetration hazard becomes relatively more important than breathing for high boiling point liquids, which have lower vapor pressures. 

The following example shows how the results in Table 12.2 together with Equation 12.10 can be used to estimate fill times. A single skin part is chosen with a rectangular shape and a surface area of 2 x 3 m. The permeability of the fabric, the fiber volume fraction, the viscosity of the resin, and the injection pressure are assumed to be known ... 

The skin is the largest organ of the body and offers a lot of opportunities for passive delivery of drugs under appropriate conditions into the underlying systemic circulation. The surface area of the skin for a typical adult weighing, say, 90 kg and 180 cm tall is approximately 2 m2 (data derived from the Geigy Scientific Tables, 3,... 

The skin of an average adult presents a surface area of about 18,000 cm2. It is a multi-layered collagenous complex(epidermis, dermis) which is relatively impermeable to most materials. However, given the right conditions of solvent and specific skin surface, the skin presents a very accessible route for drug application. Some of the latest research and development (R D) efforts of major pharmaceutical firms has been in the area of transdermal applications. 

After oral administration, griseoftilvin is absorbed from the gastrointestinal tract and deposited in new epithelial cells that make up skin, hair, claws, and nails. The drug has a greater affinity for diseased skin than for normal skin. Increasing tlie surface area of the griseoftilvin particles and the dietary fat intake also increases drug absorption. 

Numerous methods have been utilized to actually measure the amount of pesticide which impinges on the skin. One of the more widely used ones involves attaching absorbent patches to various areas of the body and analyzing the patches for pesticide on termination of the spray operation. The concentration on the patch can then be extrapolated to the surface area of the body from which it was removed. The assumptions are that the pesticide will adhere to the patch in the same manner as it would to skin, that the distribution of the pesticide will be uniform over the area represented by the patch and that dermal contact occurs only on exposed skin surfaces and not on skin covered by clothing (6). 

Leather is a very complex and heterogeneous substrate. Once the animal has been slaughtered, the hide or skin has to be removed, cleaned, depilated, and tanned in the so-called beam house process. The term hide is used for the outer covering of animals with a body surface area of more than 1 m2 like bovines, and the term skin for that of smaller animals like sheep, goats, and pigs. Large proportions of sheepskins are used for fur production. 

The pulmonary system and skin constitute the major routes of entry for xenobiotic materials into the body. The skin has a large surface area of up to two m2 for adults. This large area, along with skin s external exposure, means that it is a common site of contact with toxic substances, especially in the workplace. It has been estimated that about one third of all reported occupational exposures to toxic substances is through skin, and much larger numbers that produce relatively minor symptoms remain unreported.5 Skin maladies constitute a large fraction of occupational and consumer problems with industrial chemicals and consumer products. 

The flow-through cell consists of a Teflon receptor cell with an exposed skin surface area of 0.32 cm2 and a receptor cell volume of 0.13 ml. Sink conditions are maintained by pumping phosphate-buffered saline under the skin in the receptor cell at about 3 ml/hr. Thus, the receptor volume is replaced about 23 times per hour. These cells are then mounted on a water-jacketed bracket which maintains the receptor solution in the cells at 33°C. The receptor media which is pumped under the cells is degassed in order to reduce air bubble formation under the skin. 

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