## 4 Discussion
### Heads: Impact of Age on Cr(VI) Neurotoxicity  
Ours is the first study to consider different ages in Cr(VI) neurotoxicity, and these data are summarized in Supplementary Table S3. Throughout this study, we observed notable age differences in Cr(VI) effects on female grip strength, locomotor coordination, anxiety, spatial memory, sociability, and social novelty preference. In the context of our previous study, we observed sex differences in Cr(VI) effects on these behaviors in rats of the same age (e.g., young females vs. young males). Here, we discuss age and sex differences in Cr(VI) neurotoxicity. Cr(VI) had no effect on female grip strength after 1 week, but we observed age differences in Cr(VI) effects on grip strength after 7 weeks. Young and middle-aged females exhibited decreased grip strength, directly contrasting a significant increase in geriatric females. Regarding sex differences, males exhibited significant changes in grip strength after 1 and 7 weeks of Cr(VI) exposure. Young males also exhibited decreased grip strength after 1 week of exposure, and this decrease was significant after 7 weeks, but exhibited a stronger effect than young females. After 7 weeks, middle-aged males exposed to 0.05 mg Cr(VI)/L exhibited significantly increased grip strength, which contrasted the decrease we observed for females exposed to 0.05 mg Cr(VI)/L. Geriatric males exhibited a concentration-associated increase in grip strength at both time points, which was a stronger effect than what we observed in females. Age-related changes in Cr(VI) effects on grip strength are intriguing and puzzling, though the effects are mostly consistent across sexes. Cr(VI) impaired grip strength in male and female spatiatric rats. It is possible that an age-related decrease in stomach and ileum pH may enhance the reduction of Cr(VI) to Cr(III) [54]. Some studies have reported that Cr(III) supplementation may be beneficial to muscle performance, thus improving grip strength in geriatric rats [55]. We assessed locomotor function using an open-field assay and observed age differences in female rats exposed to Cr(VI) for motor coordination (rearing) and locomotor function (distance traveled). We observed no change in rearing by young females after 2 or 8 weeks, but we observed an increase in middle-aged and geriatric females after 2 weeks. After 8 weeks, this effect was not apparent in geriatric females and reversed in middle-aged females. We observed no change in distance traveled by females in any age group after 2 weeks, but we observed slightly decreased distance traveled in geriatric females exposed to 0.05 mg Cr(VI)/L after 8 weeks. Regarding sex differences in locomotor function, we observed overall greater rearing counts and distance traveled by females compared to males. Cr(VI) decreased rearing in young males after 2 and 8 weeks of exposure, contrasting the lack of an effect in young females. While sex differences in young rats' rearing behavior are not reported in the Cr(VI) literature, other data suggest young females may be less vulnerable to chemical-induced locomotor impairment than young males [56; 57]. In middle-aged rats, we observed a greater reduction in rearing behavior following Cr(VI) exposure in females than in males. These data may suggest vulnerability to the effects of Cr(VI) on locomotor function changes with age, and this age-related vulnerability is distinct between sexes. We observed age-related differences in anxiety using the open-field assay and elevated plus maze. After 2 weeks of Cr(VI) exposure, we observed increased center area exploration in the open-field assay by young females exposed to 0.1 mg/L and middle-aged females exposed to 0.05 mg/L, but a slight decrease in geriatric females exposed to 0.1 mg/L. During the later open-field test (8 weeks), we observed an attenuation in the Cr(VI) effect on young females, no apparent effect in geriatric females, and a reversed effect in middle-aged females exhibiting less center exploration.