Effect of acetamiprid on the immature murine testes

Abstract

Neonicotinoids, such as acetamiprid (ACE), a pesticide used worldwide, are believed to be safe for human use. These molecules are structurally similar to nicotine, act as nicotinic acetylcholine receptor (nAChR) agonists, and were shown to be associated with neuromuscular and reproductive disorders, but these experiments were primarily performed in mature animals. In this study, the effects of ACE on the testes of immature mice were examined. The exposure of 3-week-old mice to ACE-containing water for 180 days led to a decrease in body weight and mildly affected spermatogenesis. Additionally, the expression of testosterone-metabolism genes, nAChR subunit genes, and proliferation-associated genes decreased in the testes of ACE-treated mice. Our results show that immature rodents may be less sensitive to ACE than mature ones, that mice may be more likely to accumulate ACE than rats, and that the development of disorders may be affected by the accumulation of ACE in the testes.

Statement on the active substance acetamiprid

“…Five in vivo experimental studies were notified. The assessment endpoints categories identified were neurotoxicity (RefID 4 – Terayama et al, 2016 ), endocrine disruption (RefID 2 – Kong et al, 2017 and RefID 5 – Terayama et al, 2018 ), immunotoxicity (RefID 3 – Marzouki et al, 2017 ) and DNT (RefID 6 – Kagawa and Nagao, 2018 ).…”

“…Therefore, it was concluded that an EKE was needed to assess the impact of the new submitted studies on the current EFSA and ECHA conclusions. Two in vivo studies in animals provided relevant data (Kong et al, 2017 ; Terayama et al, 2018 ). The analysis of the data for the assessment endpoint category endocrine disruption showed that there is uncertainty on how the systemic toxicity in these two studies was evaluated and its impact on endocrine function was not assessed.…”

“…With the high uncertainty associated with the histopathological evaluation (i.e. a summary table indicating the number of animals affected and the severity scores of the findings was not presented; the description of the results were based on selected pictures; the method of fixation was considered suboptimal and the authors mentioned that staging of the seminiferous epithelium was evaluated but was not reported) of the testes and the lack of hormonal measurements in mice (Terayama et al, 2018 ), there is uncertainty on whether the evidence provided in the paper could be assessed as adverse and how to link them to an endocrine mode of action. There is evidence in the two studies of modulation of protein levels and gene expression related to testosterone synthesis.…”

“…However, the histological assessment was considered not representative of a testosterone‐mediated effect. In the mice study (Terayama et al, 2018 ), the effect was inconsistent, because there was no measurement of the circulating hormones, but there was evidence of a decrease in the testosterone synthesis (through measurement of the steroidogenic enzymatic processes). This evidence was not associated with an increase in transcript for LH‐β and for Follicle Stimulating Hormone subunit Beta FSH‐β in the pituitary gland.…”

“…Therefore, there is uncertainty on how at these doses the effect is of sufficient magnitude to disrupt the HPG axis. Terayama et al ( 2018 ) expressed the doses as mg/day per mouse. Recalculation by mg/kg bw per day, resulted in a low dose of around 104–86.6 mg/kg bw per day and a high dose of 864–720 mg/kg per day.…”