Organ system studies endocrine

The ICH S7A guidance states that "supplemental" studies are meant to evaluate potential adverse pharmacodynamic effects on organ systems functions that are not acutely essential for the maintenance of human life and not addressed by the "core battery" or repeated dose toxicity studies when there is a cause for concern.25 Examples of physiological functions that fall into that category include, but are not limited to, the renal/urinary, immune, GI, endocrine and autonomic nervous systems. This section focuses on the renal and GI systems based on their potential impact on the clinical development program. 

Tributyltin (TBT) is one of the best-studied endocrine disrupting compounds in invertebrates (Oberdorster and Cheek 2000). Concentrations as low as 1 ng/1 of TBT can lead to the development of male sex organs in female snails. This imposex response has been identified in approximately 150 species of gastropods and is clearly due to an interference with some part of the molluskan endocrine system. The toxicity of TBT to gastopods has caused its regulation. 

Age is an important factor in the assessment of toxic effects on endocrine organs. The developing endocrine system in immature animals appears to be generally more susceptible to toxic compounds than in mature animals— particularly the pituitary-gonadal axis. For some studies, it may be preferable to use male rather than female animals, thus avoiding the several metabolic effects of the estrus cycle. 

These major organ systems must be studied because growth deficits are likely to appear only secondary to effects on specific organs or tissues and may not appear for some time after nutritional insult. For example, slow or inadequate growth is a common denominator of impaired gastrointestinal function, but it does not identify the function that is impaired. In addition, some organ systems (e.g., immune and endocrine) are immature at birth every effort must be made to ensure that ingredients new to infant formulas will not affect the development of these systems or the expression of their function. 

FIGURE ES-5 Proposed levels of assessment for clinical studies of major organ, immune, and endocrine systems algorithm. [ ] = a state or condition, < > = a decision point, =... 

Numerous physiological and environmental factors such as age, stress, nutritional deficiency, and infections may affect the immune system (Sullivan, 1989). Thus, adverse findings in animal studies may reflect these indirect immunotoxic effects rather than the direct immunotoxic potential of a chemical or drug. Indirect immunotoxic effects may be assessed through histopathologic evaluations of endocrine organs such as the adrenals and pituitary. 

Let us share an example. The body s hormone system is called the endocrine system. Endocrine comes from a Greek prefix that means within (endo-) and a Greek root word that means separate (krineiri). This makes sense when you realize that hormones are substances that carry instructions between separate organs within your body. By adding the suffix -ologist (which means one who studies) to... 

If the agent possessed useful activity, it would be further studied for possible adverse effects on other major organs, including the respiratory, gastrointestinal, endocrine, and central nervous systems. 

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