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The effect of route, vehicle, and divided doses on the pharmacokinetics of chlorpyrifos and its metabolite trichloropyridinol in neonatal Sprague-Dawley rats.

Authors
Marty-MS; Domoradzki-JY; Hansen-SC; Timchalk-C; Bartels-MJ; Mattsson-JL
Source
Toxicol Sci 2007 Dec; 100(2):360-373
NIOSHTIC No.
20033013
Abstract
There is a paucity of data on neonatal systemic exposure using different dosing paradigms. Male CD (Sprague-Dawley derived) rats at postnatal day (PND) 5 were dosed with chlorpyrifos (CPF, 1 mg/kg) using different routes of exposure, vehicles, and single versus divided doses. Blood concentrations of CPF and its primary metabolite, trichloropyridinol, were measured at multiple times through 24 h. Groups included were single gavage bolus versus divided gavage doses in corn oil (one vs. three times in 24h), single gavage bolus versus divided gavage doses in rat milk, and sc administration in dimethyl sulfoxide (DMSO). These data were compared with lactational exposure of PND 5 pups from dams exposed to CPF in the diet at 5 mg/kg/day for 4 weeks or published data from dams exposed to daily gavage with CPF at 5 mg/kg/day. Maternal blood CPF levels were an order of magnitude lower from dietary exposure than gavage (1.1 vs. 14.8 ng/g), and blood CPF levels in PND 5 pups that nursed dietary-exposed or gavage-exposed dams were below the limit of detection. Single gavage doses of 1 mg/kg CPF in corn oil vehicle in pups resulted in CPF blood levels of 49 ng/g and in milk vehicle about 9 ng/g. Divided doses led to lower peak CPF levels. A bolus dose of 1 mg/kg CPF in DMSO administered sc appeared to have substantially altered pharmacokinetics from orally administered CPF. To be meaningful for risk assessment, neonatal studies require attention to the exposure scenario, since route, vehicle, dose, and frequency of administration result in different systemic exposure to the test chemical and its metabolites.
Keywords
Pesticides-and-agricultural-chemicals; Organo-phosphorus-compounds; Insecticides; Metabolic-study; Laboratory-animals; Laboratory-testing; Risk-factors; Risk-analysis; Pesticides
Contact
Mary Sue Marty, Toxicology and Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, MI 48674
CODEN
TOSCF2
Publication Date
20071201
Document Type
Journal Article
Email Address
mmarty@dow.com
Funding Amount
246279
Funding Type
Grant
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-003629; Grant-Number-R01-OH-008173
Issue of Publication
2
ISSN
1096-6080
Priority Area
Research Tools and Approaches: Exposure Assessment Methods; Agriculture, Forestry and Fishing
Source Name
Toxicological Sciences
State
WA
Performing Organization
Battelle Memorial Institute, Richland, Washington
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