Developmental and neurobehavioral assessment of low-dose N-nitrosodimethylamine (NDMA) using zebrafish embryo bioassay

N-nitrosodimethylamine (NDMA) is one of the emerging nitrogenous disinfection by-products (DBPs) with probable cytotoxicity, genotoxicity, and carcinogenesis. Its potential toxicological effects have drawn considerable attention but remain inadequately known. Here two methods, including developmental toxicity evaluation and neurobehavioral toxicity evaluation, were used and compared to investigate the safety of low-dose (0, 0.1, 1, 10, 100 mu g/L) NDMA exposure to embryo-larval stage of zebrafish. Results showed that the survival and malformation rate of larvae at 6-day post fertilization (dpf) and the hatching rates at 48-h post fertilization (hpf) and 72 hpf in treatment groups had no significant difference with the control group, indicating that the tested NDMA doses were not developmentally toxic. Differently, the changes of neurobehavioral indicators performed more sensitivity. For example, 100 mu g/L NDMA exposure induced locomotor hyperactivity at 7 dpf and induced an increasing effect on the relative path angle value. Further, relative value of path angle had more consistency with locomotion results compared with absolute value, indicating that relative value of path angle may be more suitable for the safety evaluation of low-dose NDMA exposure. This work supported that zebrafish neurobehavioral test is a powerful tool in the safety assessment of low-dose NDMA exposure and also has the potential to evaluate the safety of other DBPs. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study found that low-dose NDMA exposure during the embryo-larval stage of zebrafish did not show developmental toxicity, but did impact neurobehavior, leading to increased locomotor hyperactivity and relative path angle values. The results suggest that neurobehavioral testing in zebrafish is a powerful tool for assessing the safety of low-dose NDMA exposure and potentially other DBPs.