Early biochemical detection of delayed neurotoxicity resulting from developmental exposure to chloropyrifos

Brain Research Bulletin
D E JohnsonTheodore A Slotkin

Abstract

Developing animals are more sensitive than adults to the delayed neurotoxicity caused by chlorpyrifos exposure. In developing rat brain, chlorpyrifos doses that cause no discernible systemic toxicity and only a minor degree of cholinesterase inhibition, nevertheless evoke alterations in cell function and number that appear after several days' delay. In the current study, neonatal rats were exposed to subtoxic doses of chlorpyrifos (no weight loss or mortality) on either postnatal days 1-4, or postnatal days 11-14, and the effects on cellular RNA levels were determined in two brain regions that are targeted for delayed neurotoxicity-the brainstem and forebrain. In both regions, chlorpyrifos exposure evoked significant alterations in RNA concentration and content, variables that are ordinarily very tightly controlled in the developing brain. The effects on RNA appeared well before the deficits in cell function and number and showed a regional selectivity similar to that of subsequent, delayed neurotoxicity. Deficits in RNA were more prominent in the brainstem, an early-developing brain region, than in the forebrain, which develops later. These results suggest that chlorpyrifos can elicit delayed developmental neurotoxicity by tar...Continue Reading

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Citations

Aug 17, 2005·Toxicology and Applied Pharmacology·Angela S HowardPamela J Lein
Sep 15, 2001·Brain Research. Developmental Brain Research·K W RainesT A Slotkin
Sep 15, 2001·Brain Research. Developmental Brain Research·E D LevinT A Slotkin
Oct 25, 2001·Brain Research. Developmental Brain Research·H A NavarroT A Slotkin
Mar 8, 2002·Brain Research. Developmental Brain Research·Stephanie J GarciaTheodore A Slotkin
Mar 8, 2002·Brain Research. Developmental Brain Research·T A SlotkinF J Seidler
Dec 28, 1999·Brain Research. Developmental Brain Research·K DamT A Slotkin
Mar 19, 2003·Reproductive Toxicology·Amina T FaragAhmed F El-Aswed
Sep 27, 2001·Archives of Environmental Health·J D Thrasher, K H Kilburn
Jan 1, 2003·Archives of Environmental Health·Jack D ThrasherAlan Broughton
May 11, 2002·Environmental Health Perspectives·Robin M WhyattFrederica P Perera
Dec 4, 2003·Environmental Health Perspectives·Armando MeyerTheodore A Slotkin
Nov 5, 2003·Environmental Health Perspectives·Justin E AldridgeTheodore A Slotkin
Jul 9, 2004·Environmental Health Perspectives·Robin M WhyattFrederica P Perera
Jul 9, 2005·Environmental Health Perspectives·Susan Searles NielsenHarvey Checkoway
May 7, 1999·Environmental Health Perspectives·T A Slotkin
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