Organ toxicity, target

This chapter discusses specific organ systems that contact a variety of substances in the workplace environment (or due to drug abuse and addiction), leading to health hazards. Important organs discussed here include the skin, the respiratory system, the cardiovascular system, the renal system, and the central nervous system (CNS). In the United States and other countries of the world, the application of phenol is on the increase in the manufacture of aromatic compounds, explosives, fertilizers, paints, rubber products, wood preservatives, synthetic resins, drugs and pharmaceutical products, plastics, leather tanning and 

Many chemicals are absorbed through intact skin, mucous membranes, or eyes, either by direct contact or (to a more limited extent) contact with its vapor. This is based on the irritation potential of chemicals with extensive industrial use and significant skin absorption under work conditions. 

This chapter is not an exhaustive list of all chemicals with skin-penetrating abilities. Consequently, any exclusion of a chemical from this list does not necessarily imply an inability for percutaneous absorption. When in doubt, the user should check the chemical label, material safety data sheet, manufacture date, and other details to achieve chemical safety (Table 16-1). 

Many skin diseases among occupational workers have been identified as a result of prolonged contact with irritant chemicals.1 5 In certain instances, alkylating agents, acids (sulfuric, nitric, hydrochloric, and hydrofluoric acid), and 

TABLE 16-1 Industrial Chemicals and Their Categorization as Skin Irritants 

Cadmium has been shown to be toxic to numerous organ systems in mammals, but the manifestations of toxicity vary considerably depending on the route of administration, dose and time after administration, species, gender, and environmental and nutritional factors. 

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It is important to appreciate that the magnitude of the absorbed dose, the relative amounts of bio transformation product, and the distribution and elimination of metaboUtes and parent compound seen with a single exposure, may be modified by repeated exposures. For example, repeated exposure may enhance mechanisms responsible for biotransformation of the absorbed material, and thus modify the relative proportions of the metaboUtes and parent molecule, and thus the retention pattern of these materials. Clearly, this could influence the likelihood for target organ toxicity. Additionally, and particularly when there is a slow excretion rate, repeated exposures may increase the possibiUty for progressive loading of tissues and body fluids, and hence the potential for cumulative toxicity. 

Target Organ Toxicity. This section focuses on mechanisms for sensitive health effects of major concern for lead—cardiovascular effects, hematological effects, and neurological effects, particularly in children. Bone is a major sink for lead, and there is some limited information regarding the effects of lead on bone and potential mechanisms of action. Renal effects occur at relatively high blood lead levels and evidence of renal carcinogenicity has been demonstrated only in animals mechanisms for these effects will be discussed briefly. 

Laughlin NK University of Wisconsin, Madison, Wl Validate the efficacy of chelation agents such as succimer (dimercaptosuccinic acid, DMSA) not only to reduce body lead stores in young children but also to alleviate neurobehavioral and target organ toxicity (Rhesus monkey) National Institute of Environmental Health Sciences... 

Rice, C.D., Fish immunotoxicology Understanding mechanisms of action, in Target Organ Toxicity inMarine and Freshwater Teleosts, Vol 2-Systems, Schlenk, D. and Benson, W.H., Eds., Taylor and Francis, London, 2001, 96. 

Target Organ Toxicity. -Hexane exposure is documented to cause toxicity in peripheral nerves of humans (both sensory and motor). In rats, -hexane exposure causes toxicity in the peripheral and central nervous system and in male reproductive tissues. Effects on respiratory tissue have been observed in mice and rabbits. The toxic agent in nervous system and reproductive tissues is believed to be the -hexane metabolite 2,5-hexanedione (Graham et al. 1995). 

Elucidate nature of specific types of target organ toxicities induced by repeated exposure. 

In the absence of target organ toxicity with which to set the high dose at the maximally tolerated dose, the high dose can be set at the dose that produces an area under the curve (AUC). This is 25-fold higher than that obtained in human subjects. 

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