Physiologically based pharmacokinetic model for ethyl tertiary-butyl ether and tertiary-butyl alcohol in rats: Contribution of binding to α2u-globulin in male rats and high-exposure nonlinear kinetics to toxicity and cancer outcomes.

In cancer bioassays, inhalation, but not drinking water exposure to ethyl tertiary-butyl ether (ETBE), caused liver tumors in male rats, while tertiary-butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats following exposure via drinking water. To understand the contribution of ETBE and TBA kinetics under varying exposure scenarios to these tumor responses, a physiologically based pharmacokinetic model was developed based on a previously published model for methyl tertiary-butyl ether, a structurally similar chemical, and verified against the literature and study report data. The model included ETBE and TBA binding to the male rat-specific protein α2u-globulin, which plays a role in the ETBE and TBA kidney response observed in male rats.

Development and application of a human PBPK model for bromodichloromethane to investigate the impacts of multi-route exposure.

As a result of its presence in water as a volatile disinfection byproduct, bromodichloromethane (BDCM), which is mutagenic, poses a potential health risk from exposure via oral, dermal and inhalation routes. We developed a refined human physiologically based pharmacokinetic (PBPK) model for BDCM (including new chemical-specific human parameters) to evaluate the impact of BDCM exposure during showering and bathing on important measures of internal dose compared with oral exposure. The refined model adequately predicted data from the published literature for oral, dermal and bathing/showering exposures.

Comparison of pharmacokinetics and milk elimination of flunixin in healthy cows and cows with mastitis.

Objective: To determine whether pharmacokinetics and milk elimination of flunixin and 5-hydroxy flunixin differed between healthy and mastitic cows.

Design: Prospective controlled clinical trial.

Animals: 20 lactating Holstein cows.

Development of a physiologically based pharmacokinetic model for flunixin in cattle (Bos taurus).

Frequent violation of flunixin residues in tissues from cattle has been attributed to non-compliance with the USFDA-approved route of administration and withdrawal time. However, the effect of administration route and physiological differences among animals on tissue depletion has not been determined. The objective of this work was to develop a physiologically based pharmacokinetic (PBPK) model to predict plasma, liver and milk concentrations of flunixin in cattle following intravenous (i.

Plasma pharmacokinetics and milk residues of flunixin and 5-hydroxy flunixin following different routes of administration in dairy cattle.

The objective of this study was to determine if the plasma pharmacokinetics and milk elimination of flunixin (FLU) and 5-hydroxy flunixin (5OH) differ following intramuscular and subcutaneous injection of FLU compared with intravenous injection. Twelve lactating Holstein cows were used in a randomized crossover design study. Cows were organized into 2 groups based on milk production (<20 or >30 kg of milk/d).