Developmental toxicity triggered by benzyl alcohol in the early stage of zebrafish embryos: Cardiovascular defects with inhibited liver formation and degenerated neurogenesis

Benzyl alcohol (BnOH) is an aromatic alcohol used worldwide as an excipient in foods, cosmetics, household products, and medications. Although BnOH is a bacteriostatic agent found in many parenteral preparations, this agent is responsible for precipitating the gasping syndrome in premature neonates. Increasing evidence of human exposure to BnOH and environmental contamination of BnOH requires a detailed toxicity assessment of this aromatic chemical. Few studies on the toxicity of BnOH have been reported on different animal models, but its developmental toxicity effects are not fully understood yet. Studies on the effects of BnOH on the specific endpoints of organ toxicity are rare. Thus, the present study aimed to examine the developmental toxicity effects of BnOH by using zebrafish (Danio rerio) embryo as a biological disease model. Four-hour post fertilization zebrafish embryos were exposed to BnOH for 72 h to assess BnOH toxicity on an ecological viewpoint. The median lethal concentrations of varying BnOH concentrations in zebrafish embryos were estimated. The embryonic toxicity induced by BnOH was revealed by the apoptosis in embryos and pathological alterations, such as increased mortality, inhibited hatching rate, and decreased somite number. Moreover, pericardial edema and string heartbeat were observed because of arrhythmia and cardiac malformation. The number of normal vessels in the head and trunk regions was remarkably reduced in transgenic zebrafish line Tg (Fli-1: EGFP). Morphological defects and yolk sac retention were related to the degenerated liver formation in Tg (Lfabp: dsRED). Furthermore, BnOH exposure led to the disruption of motor neuron axonal integrity and the alteration of the axon pattern in Tg (olig2: dsRED). In addition, the results exhibited the pathological effects of BnOH exposure on major organs. We believe that this study is the second to report the developmental organ toxicity of BnOH to zebrafish embryos. This study provides important information for further elucidating the mechanism of BnOH-induced developmental organ toxicity.