Toxicological Sciences, Vol 51, 265-272, Copyright © 1999 by Society of Toxicology
J Tang, RL Carr and JE Chambers
The effects of repeated oral exposures to the organophosphorus insecticide
chlorpyrifos (CPS) on brain muscarinic receptor densities, together with
cholinesterase (ChE) activity, were studied in early postnatal rats.
Initially, the effects on esterases from lactational exposure to CPS were
investigated in young rats by administering CPS (100, 150, or 200 mg/kg
subcutaneously in corn oil) to dams 1 day postpartum, yielding a
significant body burden of CPS in the dams for possible excretion in the
milk. Brain ChE inhibition in pups was less severe than in dams, whereas
liver carboxylesterase (CbxE) inhibition in pups was at the same level as
in dams. Because of the limited brain ChE inhibition obtained following
lactation, pups were exposed to CPS directly by gavage, using 3 dosing
regimens to yield a dose response. The rats were gavaged with CPS in corn
oil on alternate days from postnatal day (PND) 1 through PND 21. Rats in
the low-dosage group received 11 treatments at 3 mg/kg, those in the
medium-dosage group received 3 treatments at 3 mg/kg and 8 at 6 mg/kg, and
those in the high dosage group received 3 treatments at 3 mg/kg, 4 at 6
mg/kg, and 4 at 12 mg/kg. ChE activity in brain homogenates were inhibited
significantly by 29% and 63% in the low- and high-dosage groups,
respectively, on PND 22 and by 17% in the high dosage group on PND 40.
Muscarinic receptor densities in brain synaptosomes were reduced using
3H-N-methylscopolamine (NMS) and 3H-quinuclidinyl benzilate (QNB) as
ligands, with the effects more prominent from 3H-NMS. Densities of both
ligands recovered to the control level several days after terminating
treatment. The results indicate that pups are apparently exposed to only
limited amounts of chlorpyrifos and/or its oxon through the milk when dams
are exposed to extremely high chlorpyrifos levels. In addition, repeated
direct oral exposures of early postnatal rats to CPS will result in
persistent brain ChE inhibition and will transiently reduce muscarinic
receptor density.
ARTICLES
Changes in rat brain cholinesterase activity and muscarinic receptor density during and after repeated oral exposure to chlorpyrifos in early postnatal development
Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, MS 39762-9825, USA.
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