EHPnet: European Pollutant Emission Register

butions of exposure to environmental neuro-toxicant chemicals in the marked increase in neurodevelopmental disorders, including learning disabilities, attention deficit and hyperactivity disorder, and autism spectrum disorders (Szpir 2006). Despite the increasing recognition of the importance of evaluating developmental neurotoxicity in safety assessment (Claudio et al., the fact remains that, of > 70,000 commercial chemicals in current use, neurotoxicity of any kind has been evaluated in < 10% (Landrigan et al. 1994), and obviously, developmental neurotoxicity in a substantially smaller fraction. Even now, of the 2,000–3,000 new chemicals released each year, two-thirds never get tested for neurotoxicity, let alone developmental effects (Claudio et al. 2000), whereas between 25–40% will eventually prove to be neurotoxic (Boyes 2001). Among the many potential developmental neurotoxicants, the greatest attention has been paid to pesticides, in light of their widespread use in the home and in agriculture [U.S. Environmental Protection Agency (EPA) 2006]. Here, too, despite the institution of a standardized protocol for developmental neu-rotoxicity, few compounds have actually been tested relative to the total number of concern, even after mandated call-ins for data by the A number of factors contribute to the dearth of information on developmental neurotoxicity relative to the demonstrated need for such knowledge. First, there is the essential dichotomy between the requirement to evaluate large numbers of compounds and the costly, cumbersome protocols prescribed for standard tests in animals Second, testing compounds one at a time may produce results that are difficult to compare (Colborn 2006; U.S. EPA 2006), in large measure because the presumed mechanisms and targets are based on systemic or central nervous system effects in adults that may be unrelated to developmental neuro-The organophosphate insecticides provide an archetype. Although it was originally thought that all organophosphates act similarly through irreversible inhibition of acetylcholinesterase, it is now evident that their adverse effects on brain development actually involve multiple mechanisms, many of which are unrelated to cholinesterase inhi-Accordingly, the relative potencies of organophosphates toward cholinesterase inhibition and/or systemic toxicity do not necessarily correlate with their propensity to elicit developmental neurotoxicity (Costa 2006; One strategy proposed to resolve this problem is the use of screening techniques based on cell culture systems or lower organisms as the first stage of evaluation, thus enabling subsequent animal studies to focus on those compounds most likely to cause In the present study we use PC12 cells, a standard in vitro model for neuronal development (Teng and …