7849 The EDC Mixture “NeuroMix” Has Developmental, Anxiolytic, And Obesogenic Effects In Rats

Abstract

Abstract Disclosure: E. Morales-Grahl: None. L. M. Thompson: None. E.N. Hilz: None. A.C. Gore: None. Humans are exposed to a variety of endocrine disrupting chemicals (EDCs) on a daily basis through drinking water, food, and contact with everyday objects. Safety guidelines aim to keep exposure to individual EDCs below certain levels but don’t take into account the potentially unpredictable effects of simultaneous exposure to multiple EDCs. Furthermore, EDCs may exhibit non-monotonic dose responses. The present study assessed the effect of an EDC mixture at three different doses on two sets of behaviors implicated in EDC research: anxiety, and high fat and sugar consumption. Beginning in early pregnancy and until pups were weaned at day 21, Sprague Dawley rats were fed daily with NeuroMix, our lab’s EDC mixture containing 9 common industrial chemicals, at three doses (0.1x, 1x, 10x). The base dose (1x) contained EDCs below the no observed adverse effect level in humans (NOAEL). In adulthood, the female and male offspring were then subjected to an open field and light/dark test, followed by a high fat and high sucrose preference test. 0.1x NeuroMix exposure advanced the timing of vaginal opening in female offspring, while all doses increased anogenital distance in males, marking differences in sexual development. 1x NeuroMix exposure in male rats increased their time in the open field corners and their time immobile in the corners, indicating higher anxiety. No difference was seen in sucrose preference. Female rats exposed to 1x NeuroMix showed a higher preference for a high-fat diet, and gained more weight compared to the controls while on this diet. These findings demonstrate that a mixture of human-relevant chemicals, when administered perinatally to rats, have developmental, anxiogenic and obesogenic effects in a sexually dimorphic manner. We also show a non-monotonic response to our chemical mixture, with the 1x dose showing greater effects than the 10x dose. Overall, we provide evidence that even at levels considered safe for individual EDCs, there are adverse developmental and behavioral effects of EDCs when combined. Grant support: R35 ES035024, F32 ES034257. Presentation: 6/1/2024