Persisting neurobehavioral consequences of gestational exposure to cadmium and benzo[a]pyrene in rats

Neurotoxic risks in the environment come from many toxicants, which are often found together in complex mixtures. However, nearly all experimental studies evaluate one chemical at a time. Neurobehavioral effects of developmental exposure to heavy metals such as cadmium (Cd) and polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BaP) have been well-studied, however their potential for non-additive or interactive effects are not well known. We recently reported that, in zebrafish, embryonic exposure to the PAH benzo[a]pyrene (BaP) and/or the heavy metal cadmium chloride (CdCl₂) led to selective sub-additive effects on behavior. The current study was performed in rats, to determine whether such interactions translate to mammals and to better account for characteristics like biological sex. In this study, we exposed female rats to BAP (0.03 mg/kg/day), the metal salt CdCl₂ (0.3 mg/kg/day) or both via osmotic minipumps throughout gestation. Male and female offspring were assessed for bodily and reflex development, and locomotor, emotional and cognitive function. Cd treatment was associated with impaired sex differences in neonatal anogenital distance, enhanced negative geotaxis performance on PND7, reduced body weight at weaning, increased open-arm exploration in the elevated plus maze (females only), and reductions in sex differences in novel object recognition. Co-treatment with BaP attenuated those CdCl-effects on negative geotaxis and elevated plus maze. BaP was also associated with reduced metrics of food consumption in the novel environment suppressed feeding task, and with increases in errors during the initial phase of radial arm maze training (males only). As in zebrafish, persisting neurobehavioral effects are seen in rats after chronic developmental exposure to BaP and CdCl. However, these effects can differ between single-exposures and mixtures, which indicates a need for greater clarity on interactions within such mixtures.