Toxicants absorption

The skin is composed of an outer layer called the stratum corneum. This layer consists of dead, dried cells that are resistant to permeation by toxicants. Absorption also occurs through... 

The skin on the palm of the hand is thicker than skin found elsewhere. However, this skin demonstrates increased porosity, resulting in higher toxicant absorption. 

Sasaki, K., Takeda, M., and Uchiyama, M. Toxicity, absorption and elimination of phosphoric trimesters by killifish, Bull. Environ. Contam. Toxicol, 27(l) 775-782, 1981. 

Studying toxicity and biocompatibility of CNT is very important. Smart et al. [9] outlined directions of future research in this field. It includes pulmonary toxicity, skin irritability, macrophage response, interrelation of CNT with their toxicity, absorption, distribution and excretion, and influence of chemical functionalization of CNT on their biocompatibility. 

Contamination occurs primarily in wheat, barley, rye, and maize. Type A trichothecenes include mainly T-2 toxin, HT-2, and diacetoxyscirpenol (DAS) mycotoxins of the group B include mainly 4-deoxynivalenol (DON), commonly known as vomitoxin, and nivalenol (NIV). Toxic effects include nausea, vomiting, visual disorder, vertigo, throat irritation, and feed refusal in farm animals. The most toxic is T-2, followed by DAS and NIV, with DON being the least toxic in acute toxicity studies but the most widespread in grains worldwide and therefore the most studied. Issues related to chemical and physical data, occurrence, toxicity, absorption, distribution, and metabolism of trichothecenes are reviewed in WHO (89) and IARC (34). Physicochemical data for some selected Fusarium toxins is given by Sydenham et al. (90). The molecular structures of the main trichothecenes are shown in Fig. 9. 

As illustrated in the previous chapter, the human body can be exposed to a variety of toxicants that may be present in various environmental media such as air, soil, water, or food. However, just simply being exposed to these hazardous chemicals does not necessarily translate into a toxicological response. The mammalian body has several inherent defense mechanisms and membrane barriers that tend to prevent the entry or absorption and distribution of these toxicants once an exposure event has occurred. However, if the toxicant is readily absorbed into the body, there are still other anatomical and physiological barriers that may prevent distribution to the target tissue to elicit a toxic response. As the toxicological response is often related to the exposed dose, interactions between the toxicant and the body s barriers and defense mechanisms will have an effect on toxicant movement in the body, and ultimately modulate the rate and extent of toxicant absorption and distribution to the target tissue. 

The skin represents the largest organ in the human body, and one of its primary functions can be seen as a physical barrier to absorption of toxicants. The other major routes of toxicant entry into the body are through the respiratory and gastrointestinal tract, which can be seen to offer less resistance to toxicant absorption than the skin. In general, the respiratory tract offers the most rapid route of entry, and the dermal the least rapid. One reason for this major difference is primarily because membrane thickness, which is really the physical distance between the external environment (skin surface, air in the lung, or lumen of the gut) and the blood capillaries, varies across these portals of entry. The overall entry depends on both the amount present and the saturability of the transport processes involved. 

Immediately on entering the body, a chemical begins changing location, concentration, or chemical identity. It may be transported independently by several components of the circulatory system, absorbed by various tissues, or stored the chemical may effect an action, be detoxified, or be activated the parent compound or its metabo-lite(s) may react with body constituents, be stored, or be eliminated—to name some of the more important actions. Each of these processes may be described by rate constants similar to those described earlier in our discussion of first-order rate processes that are associated with toxicant absorption, distribution, and elimination and occur... 

Abusteit, E.O. (1983). Toxicity, Absorption, Translocation and Metabolism in Diploid and Tetraploid Soybean [Glycine max (L.) Merr.] Plants and Cell Cultures (Dissertation). Raleigh, NC North Carolina State University, p. 103. 

Acute toxicity Cumulative toxicity Absorption from various routes... 

Advanced delivery systems include transdermal patches, which are now well established and accepted by patients. Technologies under development include, for example, iontophoresis, which uses a small electric current to propel the drag through the skin. Drag delivery via iontophoresis occurs at enhanced rates and amounts in comparison to patch technology, which uses simple passive diffusion. The development of safe, non-toxic absorption enhancers to facilitate transdermal absorption is a further focus of current research. 

The vagina is a possible site for the systemic administration of various drugs. However, the low and erratic bioavailability of biopharmaceuticals via this route necessitates the use of absorption enhancers. Until safe, non-toxic absorption enhancers can be found, the route is of limited potential. A further major limitation of this route is the lack of reproducibility resulting from cyclic changes in the reproductive system. Finally, no matter what degree of optimization can be achieved via this route, it can only ever benefit approximately 50% of the population ... 

Occlusion of the skin, seen with application of water-impermeable drug vehicles or patches, alters the rate and extent of toxicant absorption. As the skin hydrates, a threshold is reached where transdermal flux dramatically increases (approximately 80% relative humidity). When the skin becomes fully hydrated under occlusive conditions, flux can be dramatically increased. This occlusive effect must be accounted for when extrapolating toxicology studies conducted under occlusive conditions to field scenarios where the ambient environmental conditions are present. Hydration may also markedly affect the pH of the skin, which varies between 4.2 and 7.3. Therefore, dose alone is often not a sufficient metric to describe topical doses when the method of application and surface area become controlling factors. Dose must be expressed as mg/cm2 of exposed skin. 

The product was also compared to Fuller s earth in a pig model. The potency of the RSDL/sponge was statistically better than Fuller s earth against skin injury induced by sulfur mustard, observed 3 days post-exposure. RSDL was more efficient than Fuller s earth in reducing the formation of perinuclear vacuoles and inflammation processes in the epidermis and dermis. The potencies of the RSDL/sponge and Fuller s earth were similar to severe inhibition of plasma cholinesterases induced by VX poisoning. Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin (Taysse et al, 2007). 

After exposure to a bioavailable toxicant, absorption takes place and the substance is distributed throughout the body or to the different compartments of the ecosystem. If the substance has high affinity for a certain structure or is lipophilic and slowly metabolized, then bioaccumulation takes place. 

A nnmber of stndies have been reported on the repeated-dose toxicity of CR following dermal administration. Owens and co-workers studied the effects of CR following mnltiple dermal application in rabbits and monkeys. In the study by Marrs and co-workers, CR in acetone was applied to the skin of mice (5 days/wk for 12 wk). The animals were kept for an additional 80 weeks following the end of the application period. No abnormalities were noted that could be attributed to CR, but a high incidence of fatty infiltration of the liver was noted in one strain of mice, which was most likely due to acetone. These investigators concluded that the repeated dermal application of CR had little effect on the skin. They further postulated that in view of the absence of any specific organ toxicity, absorption of even substantial amounts of CR would have little effect. 

It is axiomatic that, for a topically applied ehemieal to exert systemie toxicity, absorption across the dermal barrier is required. For a topieally applied eompound to be absorbed into the skin, it must first pass through the stratum eomeum, eontinue through the epidermal layers, and penetrate into the dermis, where absorption into the dermal microcirculation becomes the portal for systemie exposure. For a ehemieal with direct toxicity to the skin, systemie absorption is not required as the target eells could be any of those comprising the epidermis or dermis. 

In biology and medicine, identification and characterization of species of essential (e.g., Fe, Cu, Zn, Se), toxic (e.g., Hg, Pb, Cd, As), and therapeutic elements (e.g., Pt, Au) in living organisms is arousing great interest these days. Also, in occupational medicine, speciation provides information about the volatile species (e.g., Hg) and inhalable particles at the workplace (e.g., Cr(VI) in dust particles), providing information about trace element toxicants absorption, distribution, reactivity, toxicity, and the final excretion after an occupational exposure to Pb, Cr, As, etc. 

The answer is 2/1/1B1/. Passive diffusion (or simple diffusion) b the most common means of chemical transport. Chemicals move along a conoentiation gradient in proportion to differences in concentration. Smidl molecular wei toxicants with little charge and hi lipid solubility are transported l tiib prndpal niode of toxicant absorption. 

Ji, Yunjing, Li Janlin, Li Laiyu and Huang Zhaopei, 1988, The Study on the Toxicity, Absorption and Excretion of Mixture of Rare... 

Inhalation results in very rapid toxicity. Absorption by ingestion may be rapid but can be delayed by the presence of food in the stomach. 

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