Experimental Approaches to Studying Metabolic Fate of Xenobiotics in Food Animals

Abstract

The use of agricultural chemicals is an important aspect of animal production. Animal scientists have played an active and varied role in the recent and rapidly developed use of these chemicals. Although approval to use agricultural chemicals has always been based on both efficacy and end point residues, increased consumer concerns during the past one and one-half decades about the safety of these chemicals have caused greater awareness for the latter. In this regard, emphasis on the total residue curve of an agricultural chemical should serve as a tool that will help optimize dose rate on one hand and minimize end point residues on the other hand. Selection against lipophilic materials has resulted in a marked reduction in residue load. However, problems with lipophilic residues still exist, and knowledge about how to prevent or manage these residues in animals as well as fundamental knowledge about their absorption is needed. Continued emphasis on reducing residue load of hydrophilic chemicals through the use of devices such as implants, boluses and ear tags should have high priority as should research on the absorption and excretion mechanisms of these chemicals. There are two important areas of research that are needed to help us deal with end point residues in the future. One is better understanding of the toxicology of end point residues so we can move away from the concept of zero tolerance toward basing all of our guidelines for the use of a chemical on biological principles. The other is better understanding of the specific mode of action of the chemicals we use, which will permit more refined management of agricultural chemicals and a further assurance of safety.

Oxidative and Conjugative Metabolism of Xenobiotics by Livers of Cattle, Sheep, Swine and Rats1

“…58, No. 2, 1984 xenobiotic metabolism among species has been questioned repeatedly (Williams, 1947(Williams, , 1967(Williams, , 1974Davis et al, 1973;Caldwell, 1980Caldwell, , 1981Pacifici et al, 1981) and the need for definitive data regarding humans and livestock, as well as the species used as models, has been emphasized (Caldwell, 1980(Caldwell, , 1981Oser, 1981;Braun and Waechter, 1983;Friess, 1983;Rumsey, 1983).…”

Conditioned taste aversions

“…100 DES was used in medicine and agriculture, beginning in 1947 and 1950, respectively, and continuing through 1971 when the FDA encouraged the discontinuation of its use because of its association with vaginal and cervical cancer. 102 , 103 , 104 , 105 This usage corresponds with the increase in the incidence of anorexia nervosa in 14–20 year old females, but not other age groups, in the US and Switzerland beginning about 1965 and continuing through 1976. 106 , 107 In addition, women exposed to DES when fetuses are 5 times more likely to show inexplicable weight loss and to be diagnosed with an eating disorder such as anorexia nervosa or bulimia nervosa, compared to women who were not exposed to the drug.…”