Preweaning behaviors, developmental landmarks, and acrylamide and glycidamide levels after pre- and postnatal acrylamide treatment in rats

Abstract

At high levels of exposure, acrylamide monomer (AA) is a known neurotoxicant (LoPachin, 2004 [23]). The effects of lower levels of exposure, such as those experienced via a typical human diet, have not been widely investigated. Data at these levels are particularly relevant given the widespread human exposure through carbohydrate-containing foods cooked at high temperatures. Additionally, daily AA intake is estimated to be higher for infants and children. Earlier, we described behavioral alterations in preweaning rats resulting from developmental AA treatment (0.5-10.0mg/kg/day) (Garey et al., 2005 [14]). In the present study, the effects of lower doses were measured as well as serum AA and glycidimide (GA) levels in dams, fetuses, and young pups. Pregnant Fischer 344 dams (n=48-58/treatment group) were gavaged with 0.0, 0.1, 0.3, 1.0, or 5.0mg AA/kg/day beginning on gestational day 6 and ending on the day of parturition. Beginning on postnatal day 1 (PND 1) and continuing through PND 21, all pups/litter were gavaged with the same dose as their dam. There were no AA treatment effects on offspring fur development, pinnae detachment, or eye opening. Offspring body weight was somewhat decreased by 5.0mg/kg/day, particularly in males. However, righting reflex (PNDs 4-7), slant board (i.e., negative geotaxis) (PNDs 8-10), forelimb hang (PNDs 12-16), and rotarod behavior (PNDs 21-22) were not significantly altered by AA treatment. Male and female offspring of the 5.0mg/kg/day group were 30-49% less active in the open field at PNDs 19-20 (p<0.05). Serum AA levels of GD20 dams and their fetuses were comparable, indicating the ability of AA to cross the placental barrier. AA levels of pups were not affected by age (PND 1 and 22) or sex. In all rats, serum AA and GA levels exhibited a dose-response relationship. These data extend those of our previous study (Garey et al., 2005 [14]) and demonstrate that overt preweaning neurobehavioral effects are apparent in rats exposed to acrylamide pre- and postnatally, but only at the highest doses tested.