Neurodevelopmental effects of perinatal fenarimol exposure on rats.

Knowledge about the potential toxic effects of fenarimol, a widely used fungicide, is still limited. Fenarimol is an aromatase inhibitor and therefore can affect estrogen/androgen levels in vivo in rodents. In view of these facts, the aim of the present work was to study the effects of fenarimol maternal exposure during different critical phases in the development of central nervous system in rat pups, on early physical and neurobehavioral endpoints essential to their development. For that, the effects of the fungicide fenarimol (150 and 300 mg/kg) were examined at three different developmental stages in the rat: during the first 6 days of gestation, prenatal (15-21 days), or first 6 days of lactation. Three categories of the impact of fenarimol on neonatal growth and neurobehavioral development of offspring were assessed: (1) physical, (2) reflex and strength, and (3) motor coordination. Findings on the pups' physical development did not indicate any significant alterations of the postnatal age at which specific developmental milestones were observed (pinna detachment, development of the fur, eruption of the incisor teeth, opening of the ears and eyes and testes descent). However, there was a reduced rate of weight gain in pups of mothers treated during lactation related to the earlier testing time periods (1-23 days of life). The study of the functional state of the rat pup nervous systems at different stages of postnatal development revealed some neurodevelopmental delays in righting reflex, climbing and grip response and locomotion (20-90 days of life) in the treated groups. Taken together, findings of this study emphasize that, as a result of fenarimol maternal exposure, some neuromuscular and behavioral deficits in nursing pups may occur principally during the last gestational period and lactation. These results could be the basis for further studies on molecular actions of fenarimol in order to predict better the biological consequences of this fungicide.

Prenatal and perinatal fenarimol-induced genotoxicity in leukocytes of in vivo treated rats.

The identification of environmental compounds that have adverse effects on reproductive health and animal development is particularly challenging. Fenarimol, a systemic fungicide, is considered non or weakly genotoxic. However, its available toxicological data are controversial and incomplete. This study was conducted in rat in vivo to determine whether this compound (150 and 300 mg/kg) had adverse effects on DNA integrity in dams and pups after maternal subcutaneous exposure. The animals were exposed during early gestation (1-6 days), late gestation (last 6 days), or first 6 days of lactation. Findings on fenarimol genotoxicity showed an adverse effect when detected by the Comet assay, both in dams and pup, and state that animal sensitivity to fenarimol is higher during postnatal period. Since the DNA damage increases during the time of exposure (2 h to 6 days after the birth), our data on pups suggest that fenarimol can mainly act on cell DNA through direct exposure of litter via milk.