Developmental toxicity evaluation of three hexabromocyclododecane diastereoisomers on zebrafish embryos

Structural dissimilarities of hexabromocyclododecane diastereoisomers could raise substantial differences in physicochemical, biological and toxicological properties. In order to fully assess the environmental safety and health risk of hexabromocyclododecanes (HBCDs), zebrafish embryos were used to evaluate the developmental toxicity of individual HBCD diastereoisomers (α-HBCD, β-HBCD and γ-HBCD). Four-hour post-fertilization (hpf) zebrafish embryos were exposed to different concentrations of HBCD diastereoisomers (0, 0.01, 0.1 and 1.0 mg/l) until 120 hpf. The results showed that exposure to HBCDs can affect the development of zebrafish embryos/larvae in a dose-dependent and diastereoselective manner. The diastereoisomers α-, β- and γ-HBCD at 0.01 mg/l had little effect on the development of zebrafish embryos except that exposure to 0.01 mg/l γ-HBCD significantly delayed hatching (P < 0.05). At 0.1 mg/l, α-HBCD resulted in depressed heart rate of larvae (96 hpf) and delayed hatching, whereas β- and γ-HBCD both caused significant hatching delay and growth inhibition (P < 0.05). In addition, a remarkable and significant increase in mortality and malformation rate was noted at 0.1 mg/l γ-HBCD exposure groups (P < 0.05). At 1.0 mg/l, α-, β- and γ-HBCD significantly affected all of the endpoints monitored (P < 0.05). Additionally, HBCD diastereoisomers could induce the generation of reactive oxygen species (ROS) and the activities of caspase-3 and caspase-9 in a dose-dependent manner. The results indicated that HBCD diastereoisomers could cause developmental toxicity to zebrafish embryos through inducing apoptosis by ROS formation. The overall results showed a good agreement confirming that the order of developmental toxicity of HBCD diastereoisomers in zebrafish is γ-HBCD > β-HBCD > α-HBCD.

► We examined the effects of α-, β- and γ-HBCD on development of zebrafish embryos.
► We examined various endpoints.
► HBCDs could affect development of zebrafish embryos in a dose-dependent manner.
► We showed that α-, β- and γ-HBCD could induce apoptosis in zebrafish embryos.
► The order of developmental toxicity in zebrafish was γ-HBCD > β-HBCD > α-HBCD.