**2. Adverse effects on developing nervous system**

In human studies, prenatal exposure to 2,4-D was associated with mental retardation of the children (Casey, 1984). Comparable animal experiments in chicken and rats showed that prenatal exposure altered some behavioral patterns of the offspring (Sanders & Rogers, 1981; Sjoden & Soderberg, 1972).

In the rat, one critical period for normal maturation during growth seems to be that corresponding to the perinatal development of the brain—''the brain growth spurt'' spanning the first 3 or 4 weeks of life (Diaz & Samson, 1980). Therefore, exposure of rats to pesticides during the first weeks of life would have adverse effects on growth and behavior, as well as on the locomotor activity, as affected by anatomical changes. Noteworthy, the age at exposure is an important factor (Kolb & Wishaw, 1989).

This selective susceptibility of the developing nervous system may be due to several toxicokinetic factors and a partial lack of a blood–brain barrier (BBB) in the fetus. In humans, the BBB is not fully developed until the middle of the first year of life (Rodier, 1995).

Gupta et al. (1999) have shown that different classes of pesticides are able to change the permeability characteristics of the BBB in rats when administered during some susceptible periods of the BBB development, and that this effect may persist after exposure for variable periods. An altered BBB may render the nervous system more vulnerable to other toxics that would not be able to pass the BBB otherwise.

Therefore, although the developing nervous system has some capacity to adapt to or compensate for early perturbations, many chemical agents have been shown more toxic on the developing than on the adult nervous system (Tilson, 1998).

In the last two decades many different alterations have been reported in neonatal rats exposed to 2,4-D through breast milk, at a dose producing no overt signs of toxicity in dams. Alterations in astroglial cytoarchitecture and neuronal function (Brusco et al., 1997) as well as neuro-behavioral changes were observed in pups and adult rats after an early exposition to the herbicide (Bortolozzi et al., 1999, 2001). Other reported effects in neonate rats were a deficit in myelin lipid deposition (Konjuh et al., 2008) and changes in the ganglioside pattern in some brain regions (Rosso et al., 2000).
