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Keerthi S Guruge1, Michiko Noguchi1,2, Koji Yoshioka1
1National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
Abstract:
In this study, we evaluated the efficacy of a novel minipig strain, the Microminipig (MMPig), as an animal model for studying the pharmacokinetics of a mixture of 10 perfluoroalkyl acids (PFAAs). After a single oral dose was given, we found that the blood depuration of PFAAs (blood t1/2), which we calculated using first-order elimination curves, ranged from 1.6 to 86.6 days. Among the five body compartments analyzed, the liver was the greatest site of accumulation of perfluorooctanesulfonate and longer chain perfluorinated carboxylates such as perfluorodecanoic acid, perfluoroundecanoic acid and perfluorododecanoic acid. We observed an increasing accumulation trend of perfluorinated carboxylates in the organs associated with the fluorinated carbon chain length. The perfluorononanoic acid burden was the highest among the treated compounds 21 days after a single exposure, as 29% of the given perfluorononanoic acid dose was accumulated in the tissues. The persistence of PFAAs in edible pig tissues even after 21 days post-exposure raises concerns about the safety of swine products. This was the first study to use MMPigs to elucidate the pharmacokinetics of a group of environmental pollutants. We found that MMPigs could be excellent experimental animals for toxicological studies due to their easy handling, cost efficacy for target compounds and ease of waste treatment.
Insights
The Microminipig (MMPig) effectively models perfluoroalkyl acid (PFAA) pharmacokinetics, revealing significant PFAA accumulation in pig tissues. This highlights potential food safety concerns and the MMPig
Area of Science:
- Environmental Science
- Toxicology
- Pharmacokinetics
Background:
- Perfluoroalkyl acids (PFAAs) are persistent environmental pollutants.
- Understanding PFAA pharmacokinetics is crucial for risk assessment.
- Novel animal models are needed for toxicological studies.
Purpose of the Study:
- To evaluate the Microminipig (MMPig) as a model for PFAA pharmacokinetics.
- To investigate the accumulation and depuration of 10 different PFAAs in MMPigs.
- To assess potential food safety implications of PFAA persistence in swine.
Main Methods:
- Single oral dose administration of 10 PFAAs to MMPigs.
- Analysis of PFAA blood depuration (t1/2) using first-order elimination kinetics.
- Quantification of PFAA accumulation in five body compartments, including the liver.
Main Results:
- Blood half-lives of PFAAs ranged from 1.6 to 86.6 days.
- The liver showed the highest accumulation for specific PFAAs (e.g., perfluorooctanesulfonate).
- Perfluorononanoic acid had the highest tissue burden (29%) 21 days post-exposure.
Conclusions:
- MMPigs are suitable models for PFAA pharmacokinetic and toxicological studies.
- PFAA accumulation in edible pig tissues raises food safety concerns.
- MMPigs offer advantages in handling, cost-effectiveness, and waste management for toxicological research.
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