PFOA-induced doseand sex-dependent disruption of hematological homeostasis in Wistar rats

Abstract

Perand polyfluoroalkyl substances, including perfluorooctanoic acid (PFOA), are persistent environmental contaminants of global concern. There is evidence suggesting that PFOA exposure may contribute to disturbances in hematological homeostasis, even at low exposure levels. The aim of this study was to investigate the effects of PFOA on hematological parameters in male and female Wistar rats following exposure to low doses reflecting real-life environmental exposure. A total of 48 rats (24 per sex) were randomly assigned to three treatment groups and a control group. PFOA dose selection was based on previously published literature and included three exposure levels. Groups M1/F1 were exposed to doses corresponding to low levels of exposure in the general population, M2/F2 to doses corresponding to higher exposure levels, while M3/F3 were treated with doses based on the highest no-observed-adverse-effect levels reported in the literature. After 28 days, the animals were humanely euthanized, blood was collected via cardiac puncture, and hematological parameters were analyzed using an automated hematology analyzer. In males, a significant increase in eosinophil counts was observed in the M2 and M3 groups, together with a decrease in erythrocyte counts in M2, as well as reduced platelet counts in both higher-dose groups (M2 and M3). In contrast, females showed an opposite response, with increased erythrocyte counts in F2 and F3 groups, along with elevated hematocrit in F2. Overall, the results indicate pronounced sex-specific differences in hematological sensitivity to PFOA, with more consistent alterations observed at higher exposure levels.