Effects of oral exposure to the phthalate substitute acetyl tributyl citrate on female reproduction in mice

Acetyl tributyl citrate (ATBC), is a phthalate substitute used in food and medical plastics, cosmetics and toys. Although systemically safe up to 1000 mg kg⁻¹ day⁻¹, its ability to cause reproductive toxicity in females at levels below 50 mg kg⁻¹ day⁻¹ has not been examined. This study evaluated the effects of lower ATBC exposures on female reproduction using mice. Adult CD-1 females (n = 7–8 per treatment) were dosed orally with tocopherol-stripped corn oil (vehicle), 5 or 10 mg kg⁻¹ day⁻¹ ATBC daily for 15 days, and then bred with a proven breeder male. ATBC exposure did not alter body weights, estrous cyclicity, and gestational and litter parameters. Relative spleen weight was slightly increased in the 5 mg kg⁻¹ day⁻¹ group. ATBC at 10 mg kg⁻¹ day⁻¹ targeted ovarian follicles and decreased the number of primordial, primary and secondary follicles present in the ovary. These findings suggest that low levels of ATBC may be detrimental to ovarian function, thus, more information is needed to understand better the impact of ATBC on female reproduction.