Developmental neurotoxicity (DNT) studies are designed to investigate whether pre- or post-natal exposure to a toxicant affects neural development. Bayer conducted such a study with imidacloprid. Imidacloprid was administered in the diet to mated Sprague Dawley rats. The females were treated from gestation day 0 to 20 and then continued through the lactation day 21 at doses of 0, 100, 250 and 750 ppm, corresponding to an average daily intake of 0, 8, 19 and 54.7 mg/kg/day during gestation. The pups were indirectly exposed to imidacloprid for a total of 41 days (20 days in utero and 21 days via lactation). After weaning on postnatal day 21 pups were given untreated feed. Brain tissue from 10 pups/sex/group were analyzed on postnatal days 11 and 75. On post-natal day 11, female pups from the 750 ppm group had a decreased caudate putamen width (-5.5%) and a substantial reduction in the thickness of the corpus callosum (-27.6%). Morphometric brain measurements were not performed in the intermediate and low dose groups. The EFSA Panel on Plant Protection Products and their Residues (PPR) expressed concern about this pattern and although it does not directly demonstrate neurotoxicity, it cannot be dismissed, especially considering the magnitude of decrease in corpus callosum dimension. The major point of disagreement between Bayer Crop Science (BCS) and the PPR Panel is the interpretation of morphometric data. BCS contends that imidacloprid caused no morphometric effects in their DNT study; meanwhile BCS recognizes that their morphometric investigations were limited to the high dose and control groups. By contrast, the PPR Panel considered the morphometric data a source of concern and the lack of intermediate and low dose data as important missing information. Using the available data it is impossible to assess a dose-response relationship for morphometric changes. The level of uncertainty identified in brain morphometry precludes a robust characterization of the DNT potential of imidacloprid.
California Environmental Protection Agency - Imidacloprid Risk Characterization Document, February 9, 2006 (attached)