Short- and long-term neurobehavioral toxicity of fluorene after a nose-only exposure during the lactating period (14 days) in F1 Wistar rats

Among polycyclic aromatic hydrocarbons (PAHs), fluorene is a highly volatile compoundbeing one of the most abundant in air. Because significant fluorene concentrations have been measured in the breast milk of non-smoking women, the risk for the developing brain of a breast-feeding exposure to this compound has to be evaluated. Wistar female rats were nose only exposed to 1.5 or 150 ppb of fluorene from postnatal day 3 (PND3) to PND16 (6h/day, 14 days) whereas the controls were inhaled with clean air over the same period. Rat pups were assessed for their sensory-motor development during the first three weeks of life and for anxiety (elevated-plus maze, EPM), activity (open-field) and spatial learning (Y maze, eight-arm maze) at adulthood. Results of the tests performed before weaning showed transient delays in the maturation of motor and sensory abilities of fluorene-exposed pups compared to controls at both levels of exposure (1.5 and 150 ppb) whereas the maternal behavior of the dams towards the pups was exacerbated. At the adult stage, persistent behavioral disturbances were observed in fluorene-contaminated rats. Thus, a locomotor hyperactivity and a concomitant reduction in the level of anxiety were observed in rats exposed to 150 ppb of fluorene in the EPM and in the open-field. On the opposite, the anxiety level of rats exposed to 1.5 ppb of fluorene was significantly increased in the EPM whereas no significant modifications were detected in the open-field. In both groups, the learning abilities of the animals remained unaffected. These results show the same behavioral defects as those reported in adult rats directly exposed to fluorene (Peiffer et al., 2013) and confirm the potential neurotoxicity of this highly volatile PAH. The same exposure was performed during gestation and showed slight behavioral defects, suggesting a significant contribution of the period of exposure in the toxicity of this compound.
Peiffer J., Cosnier F., Grova N., Nunge H. Salquèbre G., Decret MJ., Cossec B., Rychen G. Appenzeller BMR., Schroeder H. (2013) Neurobehavioral Toxicity of a Repeated Exposure (14 Days) to the Airborne Polycyclic Aromatic Hydrocarbon Fluorene in Adult Wistar Male Rats. PlosOne, 8(8): e71413. doi:10.1371/journal.pone.0071413.