Hypopigmentation was the principal manifestation of systemic toxicity when the experimental platelet aggregation inhibitor, PD-89454, was orally administered to Beagle dogs for 28 days. Pigmentation changes were present in skin of nose, lips and eyelids and mucosa of hard palate. Fontana-Masson stain demonstrated decreased melanin within melanocytes and keratinocytes. Melanocytes were globoid with inconspicuous dendritic processes and had small, incompletely pigmented melanosomes that were quantitatively reduced relative to controls. Toxic mechanism of action of PD-89454, structurally distinct from known depigmenting compounds, was not established but ultrastructural findings suggest an interference in melanosome formation and/or melanization.
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