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Title: Comparative Pharmacokinetics of High and Low Doses of the Herbicide Propanil in Mice

Abstract

We have documented that the herbicide propanil is immunotoxic in mice, and our in vitro tissue culture experiments largely recapitulate the in vivo studies. Laboratory studies on environmental contaminants are the most meaningful when these studies are conducted using concentrations that approximate levels in the environment. Many techniques to measure the distribution and pharmacokinetics (PK) on compounds rely on techniques, such as liquid scintillation counting (LSC) of radio-labeled starting compound, that require concentrations higher than environmental levels. The aim of this study was to compare tissue PK after exposure to propanil concentrations more relevant to levels of exposure to agricultural workers and the general population to concentrations previously reported for laboratory studies. To this end, we conducted a study to measure propanil distribution in three immune organs, using ultrasensitive accelerator mass spectrometry (AMS). Here, we used two doses: the lower dose modeled levels expected in the environment or long-term occupational exposure to low doses, while the higher dose was to model the effects of an accidental exposure. Our results showed that the distribution and PK profiles from these two different concentrations was markedly different. The profile of the high dose (concentration) exposure was indicative of saturation of the detoxifying capabilitymore » of the animal. In contrast, at the lower environmentally relevant concentration, in vivo concentrations of propanil in spleen, liver, and blood dropped to a very low level by 720 min. In conclusion, these studies highlight the differences in PK of propanil at these two doses, which suggests that the toxicity of this chemical should be re-investigated to obtain better data on toxic effects at doses relevant for humans.« less

Authors:
 [1];  [2];  [2];  [2]; ORCiD logo [1]
  1. West Virginia Univ., Morgantown, WV (United States). Dept. of Microbiology, Immunology, and Cell Biology
  2. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Center for Accelerator Mass Spectrometry
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1479060
Report Number(s):
LLNL-JRNL-752574
Journal ID: ISSN 0893-228X; 938884
Grant/Contract Number:  
AC52-07NA27344
Resource Type:
Accepted Manuscript
Journal Name:
Chemical Research in Toxicology
Additional Journal Information:
Journal Volume: 31; Journal Issue: 10; Journal ID: ISSN 0893-228X
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Schafer, Rosana, Ognibene, Ted J., Malfatti, Michael A., Turteltaub, Kenneth W., and Barnett, John B. Comparative Pharmacokinetics of High and Low Doses of the Herbicide Propanil in Mice. United States: N. p., 2018. Web. doi:10.1021/acs.chemrestox.8b00151.
Schafer, Rosana, Ognibene, Ted J., Malfatti, Michael A., Turteltaub, Kenneth W., & Barnett, John B. Comparative Pharmacokinetics of High and Low Doses of the Herbicide Propanil in Mice. United States. doi:10.1021/acs.chemrestox.8b00151.
Schafer, Rosana, Ognibene, Ted J., Malfatti, Michael A., Turteltaub, Kenneth W., and Barnett, John B. Wed . "Comparative Pharmacokinetics of High and Low Doses of the Herbicide Propanil in Mice". United States. doi:10.1021/acs.chemrestox.8b00151. https://www.osti.gov/servlets/purl/1479060.
@article{osti_1479060,
title = {Comparative Pharmacokinetics of High and Low Doses of the Herbicide Propanil in Mice},
author = {Schafer, Rosana and Ognibene, Ted J. and Malfatti, Michael A. and Turteltaub, Kenneth W. and Barnett, John B.},
abstractNote = {We have documented that the herbicide propanil is immunotoxic in mice, and our in vitro tissue culture experiments largely recapitulate the in vivo studies. Laboratory studies on environmental contaminants are the most meaningful when these studies are conducted using concentrations that approximate levels in the environment. Many techniques to measure the distribution and pharmacokinetics (PK) on compounds rely on techniques, such as liquid scintillation counting (LSC) of radio-labeled starting compound, that require concentrations higher than environmental levels. The aim of this study was to compare tissue PK after exposure to propanil concentrations more relevant to levels of exposure to agricultural workers and the general population to concentrations previously reported for laboratory studies. To this end, we conducted a study to measure propanil distribution in three immune organs, using ultrasensitive accelerator mass spectrometry (AMS). Here, we used two doses: the lower dose modeled levels expected in the environment or long-term occupational exposure to low doses, while the higher dose was to model the effects of an accidental exposure. Our results showed that the distribution and PK profiles from these two different concentrations was markedly different. The profile of the high dose (concentration) exposure was indicative of saturation of the detoxifying capability of the animal. In contrast, at the lower environmentally relevant concentration, in vivo concentrations of propanil in spleen, liver, and blood dropped to a very low level by 720 min. In conclusion, these studies highlight the differences in PK of propanil at these two doses, which suggests that the toxicity of this chemical should be re-investigated to obtain better data on toxic effects at doses relevant for humans.},
doi = {10.1021/acs.chemrestox.8b00151},
journal = {Chemical Research in Toxicology},
number = 10,
volume = 31,
place = {United States},
year = {2018},
month = {9}
}

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