Evaluation of the developmental toxicity of leucomalachite green administered orally to rats

► The unmetabolized compound was detected in the plasma of the rat treated with LMG. ► LMG entered the amniotic fluid through the placental barrier. ► LMG at 160mg/kg/day caused embryolethality in rats. ► LMG at 80–160mg/kg/day caused fetal developmental toxicity in rats. ► In this study, the maternal and developmental toxicity NOAEL of LMG was 10mg/kg/day. Malachite green (MG) had been extensively used worldwide in the past few decades as an effective fungicide, bactericide, ectoparasiticide, and antiprotozoan on fish. It is rapidly and extensively metabolized to leucomalachite green (LMG) in fishes. To study the developmental toxicity of LMG, we evaluated the maternal and embryo/fetal effects of LMG orally administered to Sprague–Dawley rats once daily from day 6–15 of gestation at dose levels of 0, 10, 80, and 160mg/kg/day. In the current investigation, the unmetabolized compound (LMG) was detected in the plasma of the dams treated with LMG and in the amniotic fluid. At dose levels of 80 and 160mg/kg/day, LMG induced maternal toxicity, which consisted of severe reduction in maternal weight and food consumption during the treatment period. Doses of 80 and 160mg/kg/day induced fetal skeletal abnormalities. The major skeletal defects were bipartite ossification of the thoracic centrum. LMG at 160mg/kg/day also induced marked embryolethality and visceral abnormalities. Based on the results of this study, a dose level of 10mg/kg/day is considered the no-observed-adverse-effect-level (NOAEL) for maternal and fetal developmental toxicity in rats.