Pharmacokinetic and adaptation factors involved in testicular toxicity.

In the male gonads, factors that modify toxicity include the pharmacokinetic parameters governing the absorption, distribution, activation, and detoxication of toxicants; covalent binding to macromolecules; and DNA damage as well as DNA repair of damaged germ cells. All of these factors are being studied in our laboratory at the present time. The male germ cells are protected by a biological barrier comparable to that which retards the penetration of chemicals to the brain; permeability constants for the two are nearly identical. Toxication and detoxication processes are present in both the seminferous tubule and interstitial cellular compartments. The balance of toxication-detoxication processes apparently favors the germ cells; detoxication reactions are relatively more abundant in the seminiferous tubules. Unscheduled DNA repair has been shown in spermatogonia and spermatocytes; spermatids and sperm lack DNA repair capability. The DNA repair capacity associated with spermatogenic cells appears to be dose-dependent and saturable. Understanding the pharmacokinetic characteristics of the blood-testis barrier, toxication and detoxication mechanisms as well as DNA repair systems in male gonads will allow a better understanding of species comparison and reproductive and genetic toxicity. This understanding will also increase the reliability of extrapolating laboratory animal data to man and estimating human risk.