Applications of isotope differentiation for metabolic studies with di-(2-ethylhexyl) phthalate

The pervasiveness of the plasticizer di-(2-ethylhexyl) phthalate (DEHP) in the environment and especially in the laboratory results in a background that may cause severe interference with analytical studies. Animal-to-animal variability in the distribution of DEHP metabolites in excreta normally makes it necessary to use large groups of animals when different treatments are compared. Finally, radioactive tracers are usually considered undesirable for metabolic studies involving human subjects. All of these problems can be overcome through the use of multiple isotopic labels, especially 12C/13C/14C. Examples are given involving rats and monkeys, and applicability to humans is discussed. The principles involved are not limited to any particular class of test compounds. In rats, the competing pathways for metabolism of phthalate esters produce a different distribution of metabolites from a small intravenous dose of DEHP than from a large oral dose.