Early Metabolic Changes in Rat Epidermis and Dermis Following Cutaneous Application of Irritant Doses of Tributyltin

Abstract

Metabolic changes produced in rat skin by tributyltin have been determined with the aim of identifying some of the early events which may be associated with the irritant response of this compound. When the skin irritant tributyltin (TBT) was applied to rat dorsal skin as a single cutaneous dose of 67 nmoles of TBT/sp. cm, steady state levels of 0.44 nmoles/mg dry weight were attained in the viable epidermis by 1 hr. Calculations indicate that depletion of the applied dose and consequent reduction of the concentration in the viable epidermis occurred after 5–6 hr. This dose of TBT significantly reduced the oxygen consumption of epidermal slices by 1 hr. There were minimal pathological changes at this times. Maximum inhibition of oxygen consumption occurred by 8 hr (epidermal and dermal slices inhibited by 49% and 46% respectively) by which time focal epidermal and dermal separation had occurred and numerous inflammatory cells were present. Oxygen consumption returned to normal within 48 hr. The inhibition was accompanied by a concomitant reduction in ATP concentration in the epidermis with values reduced by 63% at 12 hr. ATP remained at this value for 20 hr, returning to normal by 48 hr. Lactate concentration in full thickness skin increased by 89% within 2 hr of application of tributyltin and remained elevated for up to 48 hr. The earliest detectable reductions in oxygen consumption and ATP concentration coincided with the time when the tributyltin content of the epidermis was maximal and preceded any necrotic changes. The recovery phase coincided with reduction of tributyltin concentration. It is concluded that the early toxic action of tributyltin in rat skin involves inhibition of oxidative metabolism. The resulting perturbations may result in cellular injury or dearth and these changes may be involved in production of the altered skin.