Quantitative elucidation of the transfer of the neonicotinoid pesticide clothianidin to the breast milk in mice

Developmental stage-specific exposure and neurotoxicity evaluation of low-dose clothianidin during neuronal circuit formation

“…This report is consistent with the results of the two groups exposed to CLO during the neonatal period in the present study. Newborns are nourished by breast milk, and previous reports have shown that CLO is metabolized in the mother’s body and is rapidly transferred to and concentrated in the breast milk [ 34 ]. Moreover, CLO has been reported to have adverse neurodevelopmental and neurobehavioral effects [ 12 , 13 , 14 , 23 ].…”

“…Recently, however, studies exposing birds and mammals to no-observed-adverse-effect-levels (NOAELs) of NNs have revealed that NNs affect reproduction, the thymus, gut flora, and neurobehavior in higher vertebrates [ 4 , 14 , 21 , 23 , 26 ]. Moreover, it is clear that NNs are routinely transferred from mother to offspring, considering the rapid transfer of clothianidin (CLO), a type of NN, and its metabolites from mother to fetus via the placenta [ 27 ]; the metabolism and concentration of CLO in mothers and its rapid transfer into breast milk [ 34 ]; and the detection of NNs in the urine of Japanese adults, children, and newborns [ 17 , 18 , 28 , 39 ]. The fetal and neonatal periods correspond to the most important stages in the development of brain functions.…”

No-observed-adverse-effect-level (NOAEL) clothianidin, a neonicotinoid pesticide, impairs hippocampal memory and motor learning associated with alteration of gene expression in cerebellum

“…Although NNs have been considered safe for mammals because their affinity for nAChRs is tens to hundreds of times higher in insects than in mammals, recent studies in mammals, primarily rodents, have indicated that nAChRs induce cognitive‒emotional changes, such as anxiety-like behavior and decreased spontaneous locomotor activity [ 8 , 9 , 19 , 20 , 21 , 22 , 24 , 25 , 37 , 40 , 44 , 51 , 52 , 53 , 55 , 56 , 62 ]. However, only a limited number of investigations on memory and learning in mammals have been reported, and the severity of effects at trace concentrations, along with the underlying mechanisms, remain unclear.…”

Next-generation effects of fetal and lactational exposure to the neonicotinoid pesticide clothianidin on the immune system and gut microbiota

“…Our previous study revealed that subchronic ingestion of clothianidin (CLO), a type of NN, caused a decrease in thymus weight and induced dysbiosis in rats [ 36 ], showing for the first time an association between NNs and dysbiosis in mammals. In addition, CLO and its metabolites are rapidly transferred from pregnant dam to fetus [ 34 ] and are highly concentrated in breast milk [ 43 ]. They are detected in the urine of human newborns and children [ 23 , 24 , 37 ], and the next-generation effects of NN exposure are of concern [ 28 , 32 ].…”

“…Thus, CLO’s effect on the adrenal gland is thought to be significant; CLO exposure may cause a decrease in adrenal gland weight and may also affect the immune system. The F0 generation CLO-65 group and the F1 3-week-old CLO-65 group, both of which showed decreased adrenal gland weight, were exposed to CLO directly via gel, placenta, or breast milk [ 34 , 43 ]. Therefore, it is possible that CLO’s effect was greater in these 2 groups than in the F1 10-week-old CLO-65 group, and the effect was observed as a decrease in adrenal gland weight in both groups.…”