About: Characterization of Variability in Toxicokinetics and Toxicodynamics of Tetrachloroethylene Using the Collaborative Cross Mouse Population

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About: Characterization of Variability in Toxicokinetics and Toxicodynamics of Tetrachloroethylene Using the Collaborative Cross Mouse Population Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Characterization of Variability in Toxicokinetics and Toxicodynamics of Tetrachloroethylene Using the Collaborative Cross Mouse Population
Creator	Threadgill, David Rusyn, Ivan Furuya, Shinji Sweet, Stephen Venkatratnam, Abhishek Wade, Terry Chiu, Weihsueh Cichocki, Joseph Knap, Anthony Mcdonald, Thomas
Source	PMC
abstract	BACKGROUND: Evaluation of interindividual variability is a challenging step in risk assessment. For most environmental pollutants, including perchloroethylene (PERC), experimental data are lacking, resulting in default assumptions being used to account for variability in toxicokinetics and toxicodynamics. OBJECTIVE: We quantitatively examined the relationship between PERC toxicokinetics and toxicodynamics at the population level to test whether individuals with increased oxidative metabolism are be more sensitive to hepatotoxicity following PERC exposure. METHODS: Male mice from 45 strains of the Collaborative Cross (CC) were orally administered a single dose of PERC ([Formula: see text]) or vehicle (Alkamuls-EL620) and euthanized at various time points ([Formula: see text] /strain/time). Concentration–time profiles were generated for PERC and its primary oxidative metabolite trichloroacetate (TCA) in multiple tissues. Toxicodynamic phenotyping was also performed. RESULTS: Significant variability among strains was observed in toxicokinetics of PERC and TCA in every tissue examined. Based on area under the curve (AUC), the range of liver TCA levels spanned nearly an order of magnitude ([Formula: see text]-fold). Expression of liver cytochrome P4502E1 did not correlate with TCA levels. Toxicodynamic phenotyping revealed an effect of PERC on bodyweight loss, induction of peroxisome proliferator activated receptor-alpha (PPAR [Formula: see text])-regulated genes, and dysregulation of hepatic lipid homeostasis. Clustering was observed among a) liver levels of PERC, TCA, and triglycerides; b) TCA levels in liver and kidney; and c) TCA levels in serum, brain, fat, and lung. CONCLUSIONS: Using the CC mouse population model, we have demonstrated a complex and highly variable relationship between PERC and TCA toxicokinetics and toxicodynamics at the population level. https://doi.org/10.1289/EHP788
has issue date	2017-05-30(xsd:dateTime)
bibo:doi	10.1289/ehp788
bibo:pmid	28572074
has license	no-cc
sha1sum (hex)	31fae2807695521804442fedcd3f7b9f17d0f9ea
schema:url	https://doi.org/10.1289/ehp788
resource representing a document's title	Characterization of Variability in Toxicokinetics and Toxicodynamics of Tetrachloroethylene Using the Collaborative Cross Mouse Population
has PubMed Central identifier	PMC5726344
has PubMed identifier	28572074
schema:publication	Environ Health Perspect
resource representing a document's body	covid:31fae2807695521804442fedcd3f7b9f17d0f9ea#body_text
is schema:about of	named entity 'TETRACHLOROETHYLENE' named entity 'profiles' named entity 'Clustering' named entity 'account' named entity 'Population' named entity 'POPULATION' named entity 'TOXICOKINETICS' named entity 'USED' named entity 'DID' named entity 'INCREASED' named entity 'RESULTING IN' named entity 'ACCOUNT' named entity 'EVALUATION' named entity 'METABOLITE' named entity 'ALPHA' named entity 'MICE' named entity 'REVEALED' named entity 'CLUSTERING' named entity 'FAT' named entity 'TISSUES' named entity 'AREA UNDER THE CURVE' named entity 'RANGE' named entity 'INDUCTION' named entity 'COLLABORATIVE' named entity 'OXIDATIVE METABOLISM' named entity 'POINTS' named entity 'EXAMINED' named entity 'LOSS' named entity 'BASED' named entity 'BACKGROUND' covid:arg/31fae2807695521804442fedcd3f7b9f17d0f9ea named entity 'TISSUE' named entity 'PRIMARY' named entity 'TRIGLYCERIDES' named entity 'LIPID HOMEOSTASIS' named entity 'VARIOUS' named entity 'MOUSE' named entity 'VEHICLE' named entity 'RESULTS' named entity 'EXPERIMENTAL DATA' named entity 'TRICHLOROACETATE' named entity 'LUNG' named entity 'POPULATION' named entity 'DEFAULT' named entity 'MALE' named entity 'ENVIRONMENTAL POLLUTANTS' named entity 'VARIABILITY' named entity 'COLLABORATIVE' named entity 'PERC' named entity 'HIGHLY' named entity 'HAVE' named entity 'SENSITIVE TO' named entity 'GENES' named entity 'DOSE' named entity 'USING' named entity 'MOUSE' named entity 'CROSS' named entity 'KIDNEY' named entity 'MAGNITUDE' named entity 'INCLUDING' named entity 'LACKING' named entity 'LEVELS' named entity 'TO TEST' named entity 'FOLLOWING' named entity 'EXPOSURE' named entity 'SERUM' named entity 'CYTOCHROME' named entity 'CROSS' named entity 'MG%' named entity 'RELATIONSHIP' named entity 'CHARACTERIZATION' named entity 'TCA'

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