Analysis of two guideline-compliant developmental neurotoxicity studies with imidacloprid to assist the interpretation of findings that impact global registrations

Imidacloprid is a neonicotinoid insecticide that was first registered in the early 1990's, with global registrations that include agricultural, residential and veterinary uses. In 2001, Bayer reported a developmental neurotoxicity (DNT) study with imidacloprid that complied with U.S. EPA and OECD guidelines to support global registrations. The report concluded that there were slight effects in the offspring at the highest dietary level related to general or acute (neuro)-toxicity and no evidence of DNT at any dose; however, the European Food Safety Authority (EFSA) questioned certain findings at the high dose and whether the study established a clear NOAEL. More recently, the Jai Research Foundation (JRF) independently conducted a guideline-compliant DNT study with imidacloprid for other registrants, with elements incorporated into the study design to facilitate comparison with the Bayer study that could address these issues. This paper examines the findings from both studies, in the context of an updated literature review, to address regulatory uncertainty and persistent claims from non-governmental organizations that imidacloprid is a developmental neurotoxicant. The present analysis supports the interpretation that differences in brain measurements at the high dose in the Bayer study were incidental and unrelated to treatment and that imidacloprid is not a developmental neurotoxicant.