Susceptible Target Organs

Response of an individual plant or animal species to a chemical is based on concentration length, type, and route of exposure and susceptible target organ. 

Long-Term Effects Etiologic Effects Variables of Toxic Effects Dose/Response Susceptible Target Organs Exposure Rate... 

We have developed a quantitative structure-activity model for the variations in potency among the nitrosamines and, more recently, a related model for the variation in target organ for a smaller set of nitrosamines. We are currently developing a model for interspecies variation in susceptibility toward carcinogenic nitrosamines. The model for organ selectivity requires terms for the parent nitrosamine as well as for the hypothesized metabolites while the model for potency variations contains terms only for the unmetabolized parent compound. 

We recently reported a structure-activity model for variations In target organs (12) and are currently examining the possible application of the quantitative structure-activity approach to the problem of specles-to-specles differences In susceptibility toward nltrosamlne carcinogenesis (19). These two topics will be discussed In the remainder of this presentation. 

Interspecies Variations in Susceptibility. An Important assumption in the development of both the structure-potency model (eq, 1) and the structure-target-organ model (eq, 2) was that all of the test compounds were administered at equal daily... 

People with Neurologic Dysfunction or Kidney Disease. This population is unusually susceptible to lead exposure. The neurologic and renal systems are the primary target organs of lead intoxication, which may become overburdened at much lower threshold concentrations to elicit manifestations of lead intoxication (Benetou-Marantidou et al. 1988 Chisolm 1962, 1968 Lilis et al. 1968 Pollock and Ibels 1986). 

Genetically predisposed animals or induced animal models may also be used to study and predict chemical-induced autoimmunity. In induced models, a susceptible animal strain is immunized with a mixture of an adjuvant and an autoantigen isolated from the target organ. Examples are adjuvant arthritis (AA), experimental allergic encephalomyelitis (EAE) and experimental uveitis in the Lewis strain rat. Examples of spontaneous models... 

The kidney and liver are the primary target organs for hexachloroethane based on the results of toxicity testing and supported by toxicokinetic information from tissue distribution and binding studies (Lattanzi et al. 1988). Male rats were more susceptible to kidney damage than female rats (NTP 1989), and the kidneys of male rats contained 4-45% more hexachloroethane radiolabel than the kidneys of female rats (Gorzinski et al. 1985). However, there were some effects on kidneys of both sexes. 

A susceptible population will exhibit a different or enhanced response to -hexane than will most persons exposed to the same level of -hexane in the environment. Reasons may include genetic makeup, age, health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke). These parameters may result in reduced detoxification or excretion of u-hexane, or compromised function of target organs affected by -hexane. Populations who are at greater risk due to their unusually high exposure to -hexane are discussed in Section 5.7, Populations With Potentially High Exposure. 

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