Neurobehavioral and neurochemical effects of perinatal arsenite exposure in Sprague-Dawley rats.

Exposure to relatively high levels of inorganic arsenic (iAs) is associated with detrimental effects on human health, including cancer and diabetes. The effects of lower-level exposures are less clear, and gaps in the literature exist as to the effects of iAs exposure on neurodevelopment. The current study assessed the effects of perinatal iAs exposure on rodent neurodevelopment and behavior. Pregnant Sprague-Dawley (SD) rats were exposed to arsenite (AsIII) via oral gavage on gestational days (GD) 6 through 21, and pups were directly dosed via gavage on postnatal days (PND) 1 through 21. Dams and offspring received the same doses: 0.00, 0.10, 1.50, or 3.75 mg/kg/day. Male and female offspring underwent a battery of behavioral assessments from weaning until PND 180. Brain arsenic levels increased in a dose-dependent manner at both PND 1 and 21. Results from the behavioral tests show that pre- and postnatal AsIII exposure did not adversely affect offspring weight gain, adolescent motor and cognitive functions, or adult motor and cognitive functions in the SD rat. There were no differences in concentration of several brain proteins associated with blood-brain barrier permeability, dopamine functions, and inflammation.

Minimal effects from a single exposure to sevoflurane in adult male and female Sprague-Dawley rats.

Many people undergo procedures requiring general anesthesia each day and adverse cognitive effects have been reported in response to that anesthesia. Postoperative Cognitive Dysfunction (POCD) may occur in as many as 80% of adults during the first post-surgical week and can have lasting effects. Here, the cognitive and motor effects of sevoflurane exposure in Sprague-Dawley rats was examined along with body weights, blood oxygen saturation, heart rate, and body temperature. Male and female rats were exposed to 2.5% sevoflurane or medical grade air for one hour at postnatal day 115. Beginning the following day, rats began a series of behavioral tests examining locomotor activity, motor coordination, novel object recognition, and spatial learning and memory in a water maze. Blood oxygen saturation, heart rate, and body temperature were not affected by the sevoflurane exposure. A slight effect on locomotor activity was detected, but no effects on motor coordination, novel object recognition, or spatial learning and memory were observed. Brain weights following behavioral testing did not differ. The results reported here along with existing literature suggest sevoflurane is largely without effects on later cognition in adult rodents when exposure is of a relatively short duration and at a relatively low concentration.

Effects of intravenous and oral di(2-ethylhexyl) phthalate (DEHP) and 20% Intralipid vehicle on neonatal rat testis, lung, liver, and kidney.

The highest human exposures to the plasticizer di(2-ethylhexyl) phthalate (DEHP) occur through intravenous (iv) exposure from medical procedures. Rodent toxicity studies, mainly using oral exposures, have identified male reproductive toxicity after developmental exposure to DEHP as the primary concern. Other organs are also affected by DEHP and route may influence the degree of target organ involvement. Cammack et al. (2003) reported a critical study focused on testicular toxicity using oral and iv exposures of neonatal Sprague-Dawley rats to 60, 300, or 600 mg/kg body weight/day DEHP in Intralipid vehicle. The present study followed the same dosing paradigm and included assessment of additional organs to evaluate the potential utility of this design for DEHP alternatives. Reduction of testis weight was observed in all DEHP treatment groups and germ cell and Sertoli cell toxicity was observed at the two highest doses with both routes. Lung granulomas occurred in all iv DEHP groups, possibly related to increased fat particle size in DEHP lipid emulsions. Lung alveolar development was inhibited after both oral and iv high dose DEHP. Toxicity of oral Intralipid vehicle was observed in germ and Sertoli cells. The lack of such effects after iv vehicle exposure suggested that this may be a gut-mediated effect.

Developmental neurotoxicity of inorganic arsenic exposure in Sprague-Dawley rats.

High levels of inorganic arsenic (iAs) exposure are associated with severe health effects. Less clear are effects of lower exposure levels on neurodevelopment. Relative to maternal intake, there is limited lactational transfer of arsenic in humans or rodents, yet there are few rodent studies which directly exposed preweaning animals. To more clearly determine iAs developmental neurotoxicity, 28 pregnant Sprague-Dawley rats were exposed to arsenate (AsV) via drinking water (0, 23.6, 47.7, 71.0 ppm) (n = 5-7/group) from gestational day (GD) 6 through GD 22 with targeted doses of 0, 2.33, 4.67, 7.00 mg/kg/day, respectively. Offspring were dosed by gavage daily with the same mg/kg AsV dose as intended for their dam from postnatal day (PND) 1 to 21. Gestational water intake was reduced at all AsV doses, but returned to control levels on lactational day (LD) 1 when control water was returned. Gestational body weight was reduced only at the highest dose on GD 22 and lactational body weight was unaffected. Food intake was unaffected. iAs exposure did not alter offspring body weight (PNDs 1-21) or age at fur development and bilateral ear opening. Incisor eruption, however, was significantly delayed in offspring of the 4.67 and 7.00 mg/kg groups. Further, all iAs groups were significantly delayed in bilateral eye opening. Righting reflex (PNDs 3-6) was unaffected, while slant board performance (PNDs 8-11) was significantly poorer at the highest dose. Brains of culled pups (PND 1) showed dose-dependent increases of iAs. There were no significant AsV-related effects on PND 21 brain regional concentrations of dopamine, DOPAC, HVA, 5-HT or 5-HIAA. These hazard identification results will guide the study designs of developmental iAs exposure at human-relevant levels essential for risk-assessment.

Developmental treatment with bisphenol A or ethinyl estradiol causes few alterations on early preweaning measures.

Because bisphenol A (BPA) exposure is nearly ubiquitous, increased knowledge of its potential effects on development will enable better risk assessment and regulatory guidance. Here, Sprague-Dawley rats were reared in low exogenous estrogen environments. After breeding at adulthood, dams were gavaged on gestational days (GDs) 6-21 with vehicle (VEH), 2.5 or 25.0 µg/kg/day BPA, or 5.0 or 10.0 µg/kg/day ethinyl estradiol (EE2). Offspring were orally treated on postnatal days (PNDs) 1-21 with the same dose the dam received. Relative to the VEH group, dams of both EE2-treated groups weighed less throughout gestation and lactation. PND 1 absolute anogenital distance and anogenital index were unaltered by any treatment. Ages at fur development and eye and ear opening were unaffected by any treatment. Despite a significant treatment effect, no group was significantly different from VEH in PNDs 3-6 righting latencies; although males had shorter latencies and all latencies decreased with age. PNDs 8-11 slant board behavior was unaffected by any treatment; however, males had shorter turning latencies and latencies decreased with age. Preweaning body weights of BPA- and EE2-treated groups as well as naive controls were less than VEH. No treatment affected PND 21 whole or regional brain weights or levels of estradiol, testosterone, corticosterone, T3, T4, luteinizing hormone, ghrelin, or leptin. These results add to the literature indicating that developmental BPA treatment at these doses has no effects on gestational or lactational body weight, offspring anogenital distance, preweaning behaviors or hormone levels, and whole and regional brain weights measured at weaning.