Gastrointestinal tract, toxicology

Toxicology. Propionic acid is an irritant to skin, eyes, and mucous membranes. Propionic acid is a normal intermediary metabolite during the oxidation of fatty acids. It occurs ubiquitously in the gastrointestinal tract as an end product of microbial digestion of carbohydrates. It represents up to 4% of the normal total plasma fatty acids. ... 

Toxicology. Thallium is one of the most toxic of the heavy metals it primarily affects the nervous system and gastrointestinal tract and causes hair loss. 

Since the first series of compounds were poorly soluble in water, the next crucial phase of the project set out to increase the water solubility of the drug candidates in order to increase absorption from the gastrointestinal tract. Further refinements led to a candidate that was not only well absorbed when administered orally to animals, but also had outstanding antimalarial profiles both in vitro and in vivo. In comparison to available semi-synthetic artemisinins, the drug candidate OZ 277 (Scheme 27) exhibits structural simplicity, an economically feasible and scalable synthesis, superior antimalarial activity and an improved pharmaceutical profile. The toxicological profiles are also acceptable and this drug candidate entered first into man studies during 2004. 

There is considerably less information available on the toxicology of HDl after oral exposure compared to the data available on the inhalation toxicology of HDl discussed in the previous section of this profile. Clearly, inhalation is the major route of occupational exposure to HDl however, given exposure routes such as the lung mucocilliary clearance pathways, a very small amoimt of HDl could eventually enter the gastrointestinal tract and be presented for absorption, with possible systemic effects. Most of the information available on the oral absorption of HDl is about relatively large doses of HDl administered to laboratory animals, with no information located on the health effects of HDl in humans after oral exposure. 

Another technique is to monitor drug or toxicant excretion rather than blood concentrations, especially when blood or plasma concentrations are very low. Using the same equations, the AUC is now replaced by chemical concentrations in urine, feces, and expired air. Some chemicals are primarily excreted by the kidney and urine data alone may be necessary. The rate and extent of absorption are clearly important for therapeutic and toxicological considerations. For example, different formulations of the same pesticide can change the absorption rate in skin or gastrointestinal tract, and not bioavailability, but can result in blood concentrations near the toxic dose. Also different formulations can result in similar absorption rates but different bioavailability. 

Walsh, C.T. 1990. Anatomical, Physiological, Biochemical Characteristics of the Gastrointestinal Tract. Iln T.R. Gerrity and C.J. Henry, Eds., Principles of Route-to-Route Extrapolation for Risk Assessment, pp 33-50. Elsevier New York, N.Y.Wester, R.C., and H.I. Maibach. 1997. Toxicokinetics Dermal Exposure and Absorption of Toxicants. In I.G. Sipes, C.A. McQueen, and A.J. Gandolfi, Eds., Comprehensive Toxicology Volume General Principles (J. Bond, volume editor), pp. 99-114. Pergamon Press, New York, N.Y. 

Very little information is known about the absorption of acrolein following oral exposure. Based on toxicological effects observed after oral administration of acrolein, it is assumed to be absorbed through the gastrointestinal tract. However, the rate and extent of absorption are not known. 

CONSENSUS REPORTS Reported in EPA TSCA Inventory. EPA Genedc Toxicology Program. Cyanide and its compounds are on the Community Right-To-Know List. SAFETY PROFILE Poison by intraperitoneal route. Moderately toxic by ingesdon. Causes irritadon of the gastrointestinal tract. An herbicide. It is said to be slowly metaboUzed in the body to cyanide but does not have high toxicity of cyanides. When heated to decomposidon it emits very toxic fumes of CN and K2O. 

Last but not least, caution should be applied when extrapolating severe DLT or moribundity observed in toxicology studies to human because in humans intervention/treatment will be immediately applied when DLT is observed to prevent a more serious event. For example, oncologists are very adept in managing the challenge associated with myelosuppression and/or gastrointestinal tract injury that in nonclinical studies would induce a moribund condition. 

Figure 1 The anatomy of the gastrointestinal tract. (Reproduced from Smith RP (1992) The anatomy of the gastrointestinal tract. A Primer of Environmental Toxicology, p. 70. Philadelphia Lea Febiger, with permission from Lea Febiger.)...

Intestinal tract is the portal of entry for many xenobiotics such as orally administered pharmaceuticals, dietary constituents, and contaminants and even for ophthalmic drugs applied on the cornea and drained via uveoscleral tube to nasopharynx and gastrointestinal tract. Obviously it is difficult to find proper representative cells for the whole length of intestinal tract, but if the focus is on the absorption and metabolism, the colonic cell line Caco-2 has been used for decades and its characterization provides a good example of the difficulties associated with extrahepatic cell lines. Principally in food research area, several human cell lines, e.g., HIEC-6, H4, and H4-1, have been employed for bioaccessibility, absorption, and biotransformation studies [28, 29], but their application in toxicological research has been relatively unexplored. 

Williams and Wilkins, 1996. ISBN 06-8330-0318. Organized into five major sections principles of poison management, drugs, the home, chemicals, and natural toxins. There are chapters on AIDS and antiviral drugs, drug toxicology, blood transfusions, cytokines, plasma volume expanders, the gastrointestinal tract, etc. 

---