An Invertebrate Model of the Developmental Neurotoxicity of Insecticides: Effects of Chlorpyrifos and Dieldrin in Sea Urchin Embryos and Larvae
Subject: Effects of Chlorpyrifos and Dieldrin in Sea Urchin Embryos and Larvae
Date: Sat, 4 Aug 2001 11:36:13 -0400
From: Stephen Tvedten <steve@getipm.com>
Organization: Get Set Inc. (www.getipm.com)
To: Paul Helliker <phelliker@cdpr.ca.gov>
Director, State of
California, Department of Pesticide Regulation
cc: Christine Whitman whitman.christine@epa.gov
Dear Mr. Helliker, I thought you might like to read an article from: Environmental Health Perspectives Volume 109, Number 7, July 2001
An Invertebrate Model of the Developmental Neurotoxicity of Insecticides: Effects of Chlorpyrifos and Dieldrin in Sea Urchin Embryos and Larvae
Gennady A. Buznikov,1 Lyudmila A. Nikitina,1 Vladimir V. Bezuglov,2 Jean M. Lauder,3 Stephanie Padilla,4 and Theodore A. Slotkin5
1N.K. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia;
2Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia;
3Department of Cell Biology and Anatomy, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA; 4National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 5Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA
---------- Abstract Chlorpyrifos targets mammalian brain development through a combination of effects directed at cholinergic receptors and intracellular signaling cascades that are involved in cell differentiation. We used sea urchin embryos as an invertebrate model system to explore the cellular mechanisms underlying the actions of chlorpyrifos and to delineate the critical period of developmental vulnerability. Sea urchin embryos and larvae were exposed to chlorpyrifos at different stages of development ranging from early cell cleavages through the prism stage. Although early cleavages were unaffected even at high chlorpyrifos concentrations, micromolar concentrations added at the mid-blastula stage evoked a prominent change in cell phenotype and overall larval structure, with appearance of pigmented cells followed by their accumulation in an extralarval cap that was extruded from the animal pole. At higher concentrations (20-40 µM), these abnormal cells constituted over 90% of the total cell number. Studies with cholinergic receptor blocking agents and protein kinase C inhibitors indicated two distinct types of effects, one mediated through stimulation of nicotinic cholinergic receptors and the other targeting intracellular signaling. The effects of chlorpyrifos were not mimicked by chlorpyrifos oxon, the active metabolite that inhibits cholinesterase, nor by nonorganophosphate cholinesterase inhibitors. Dieldrin, an organochlorine that targets GABAA receptors, was similarly ineffective. The effects of chlorpyrifos and its underlying cholinergic and signaling-related mechanisms parallel prior findings in mammalian embryonic central nervous system. Invertebrate test systems may thus provide both a screening procedure for potential neuroteratogenesis by organophosphate-related compounds, as well as a system with which to uncover novel mechanisms underlying developmental vulnerability. Key words: acetylcholine, chlorpyrifos, cholinergic receptors, development, dieldrin, GABA, neurotoxicity, organophosphate pesticides, sea urchin. Environ Health Perspect 109:651-661 (2001). [Online 20 June 2001]
<http://ehpnet1.niehs.nih.gov/docs/2001/109p651-661buznikov/abstract.html>http
://ehpnet1.niehs.nih.gov/docs/2001/109p651-661buznikov/abstract.html
Address correspondence to T. Slotkin, Department of Pharmacology and Cancer Biology, Box 3813 DUMC, Duke University Medical Center, Durham, NC 27710-3813 USA. Telephone: (919) 681 8015. Fax (919) 684 8197. E-mail: <mailto:t.slotkin@duke.edu>t.slotkin@duke.edu
This research was supported by U.S. Public Health Service ES10356, ES10387, ES10159 and by the Russian Foundation for Basic Research (project #99-04-48514).
We thank D. McClay, Duke University, for helpful comments and D.L. Hunter, U.S. Environmental Protection Agency, for assistance with the chlorpyrifos oxon assays.
This paper has been reviewed by the Health Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the U.S. Environmental Protection Agency, and mention of trade names of commercial products does not constitute endorsement or recommendation for use.
Received 17 October 2000; accepted 4 January 2001.
Well Mr. Helliker, Who permitted you to permit? Who registered you to "register"? Who will be responsible for all that you have permitted and/or "registered"?
Respectfully, Stephen L. Tvedten
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