EFSA PPR panel expresses concern about a Bayer developmental neurotoxicity study with imidacloprid

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)
EFSA (attached)

Henk Tennekes

Sat, 05/09/2015 - 13:01

Bayer CropScience apparently refuses to conduct morphometric brain measurements in the intermediate and low dose groups, contendng that the decreased caudate putamen width (-5.5%) and a substantial reduction in the thickness of the corpus callosum (-27.6%) in female pups at the high dose on postnatal day 11 were unrelated to treatment. Corpus callosum size correlates positively with verbal memory capacity and semantic coding test performance. Children with dyslexia tend to have smaller and less-developed corpus callosums than their nondyslexic counterparts. Recent studies have also linked possible correlations between the size of the corpus callosum and autism spectrum disorders. The studies and the theory are the work of Marcel Just, Ph.D., D.O. Hebb Professor of Psychology at Carnegie Mellon University in Pittsburgh, Pennsylvania, and Nancy Minshew, M.D., Professor of Psychiatry and Neurology at the University of Pittsburgh School of Medicine and their colleagues. The research was conducted by the Collaborative Program of Excellence in Autism, a research network funded by the NICHD and the National Institute on Deafness and Other Communication Disorders. Autism may involve a lack of connections and coordination in separate areas of the brain. In people with autism, the brain areas that perform complex analysis appear less likely to work together during problem solving tasks than in people who do not have the disorder, report researchers working in a network funded by the National Institutes of Health. The researchers found that communications between these higher-order centers in the brains of people with autism appear to be directly related to the thickness of the anatomical connections between them. In essence, the extent to which the two key brain areas (prefrontal and parietal) of the autistic participants worked in synchrony was correlated with the size of the corpus callosum. The smaller the corpus callosum, the less likely the two areas were to function in synchrony. In the normal participants, however, the size of the corpus callosum did not appear to be correlated with the ability of the two areas to work in synchrony.

Sources: Medical News Today, 16 July 2006
Kozlovskiy, S.A.; Vartanov, A.V.; Pyasik, M.M.; Nikonova, E.Y. (2012). Functional role of corpus callosum regions in human memory functioning. International Journal of Psychophysiology 85 (3): 396–7. doi:10.1016/j.ijpsycho.2012.07.092