Dermal absorption/toxicity mechanism

A safer and potentially more reliable antagonist to white phosphorus dermal absorption is a solution of silver nitrate (AgN03). The mechanism is not known with certainty (Song et al. 1985) but is hypothesized to be formation of Ag3P, the toxic properties of which are not reported. 

Systemic and Local Skin Effects Exposure Considerations Even without exploring directly the mechanisms of dermal absorption, external dermal exposure has different implications for compounds that may produce systemic effects (such as cancer or toxic effects in remote tissues) and for those that act... 

Little is known about the specific biochemical mechanism(s) by which selenium and selenium compounds exert their acute toxic effects. Long-term effects on the hair, skin, nails, liver, and nervous system are also well documented, and a general theory has been developed to explain the toxicity of exposure to excess selenium, as discussed below. Generally, water-soluble forms are more easily absorbed and are generally of greater acute toxicity. Mechanisms of absorption and distribution for dermal and pulmonary uptake are unknown and subject to speculation, but an active transport mechanism for selenomethionine absorption in the intestine has been described (Spencer and Blau 1962). The mechanisms by which selenium exerts positive effects as a component of glutathione peroxidase, thioredoxin reductase, and the iodothyronine 5 -deiodinases are better understood, but the roles of other selenium-containing proteins in mammalian metabolism have not been clarified. 

Dermal toxicity of pesticides is thus usually synonymous with dermal absorption since the critical adverse effect is classical OP systemic neurotoxicity (e.g cholinesterase inhibition). The major mechanism of direct pesticide toxicity to skin is generally related to immunological mechanisms, either directly with. skin immune components after topical absorption or indirectly after systemic administration. 

Drug and chemical dermal absorption typically involves experiments conducted using single chemicals, making the mechanisms of absorption of individual chemicals extensively studied (the subject of most chapters in this volume). Similarly, most risk assessment profiles and mathematical models are based on the behavior of single chemicals. A primary route of occupational and environmental exposure to toxic chemicals is through the skin however, such exposures are often to complex chemical mixtures. In fact, the effects of coadministered chemicals on the rate and extent of absorption of a topically applied systemic toxicant may determine whether... 

Two general types of methods are available for estimating human exposure to pesticides. First, direct entrapment methods involve the use of some mechanism to entrap the toxic material as it comes in contact with the person during an exposure period. The amount of entrapped toxicant, as determined by chemical analysis, is then a direct measure of the particular exposure under study. Further calculations using the kinetics of dermal absorption for the compound and formulation under study are required to arrive at the actual ateorbed dose. For the oral and inhalation routes, exposure and absorbed dose are more closely equivalent than for the dermal route. However, for precise data, absorption must be taken into account for these routes, also. Second, indirect methods are based on measurement of some effect of the compound on the exposed individual (such as blood... 

The toxicokinetics of benzene has been extensively studied. Inhalation exposure is probably the major route of human exposure to benzene, although oral and dermal exposure are also important. Absorption, distribution, metabolism, and elimination have been studied in both humans and animals. Investigations of the metabolism of benzene have led to the identification of toxic metabolites, and to hypotheses about the mechanism of toxicity. 

Absorption, Distribution, Metabolism, Excretion. Examination of Section 2.6 clearly indicates that oral administration of NDMA has been the preferred route for studying its absorption, distribution, metabolism and excretion. This is not surprising since oral administration is easier to monitor when compared to other routes. The oral route seems to be the most pertinent to study since humans are most likely to be exposed to nitrosamines orally. Toxicokinetic data with regard to dermal and inhalation exposure of NDMA are clearly lacking. Furthermore, dermal and inhalation exposures may lead to different metabolic pathways and patterns of distribution and excretion, which could account for differences in the degree of toxicity exhibited by different routes of exposure. The metabolism of NDMA in isolated microsomal preparations seems to be well understood, but studies with cultured human cells could provide additional useful information. However, exploration of the denitrosation mechanism as an alternative to a-hydroxylation requires more attention. Determination of the urinary excretion of NDMA in control human volunteers and in individuals known to consume foods with high contents of nitrosamines could provide information concerning absorption and excretion of the xenobiotic. 

On the other hand, in vivo methods are expensive and time-consuming. However, these tests not only provide rich information on the carcinogenicity, dermal, pulmonary, and gastrointestinal toxicides induced by NIR NMs, but also can evaluate the immunological, reproductive, and developmental toxicity to determine the ehronie systemic toxicity and related mechanism of NIR NMs. In addition, animal models are particularly useful to study absorption, distribution, metabolism, and elimination of NIR NMs in the body. Thus, in vivo test results are often suitable for use as a prognostic of long-term physiological effects. 

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