title: Toxicokinetics of perfluorooctane sulfonate in rabbits under environmentally realistic exposure conditions and comparative assessment between mammals and birds.
abstract: This article describes the toxicokinetics of perfluorooctane sulfonate (PFOS) in rabbits under low repeated dosing, equivalent to 0.085μg/kg per day, and the observed differences between rabbits and chickens. The best fitting for both species was provided by a simple pseudo monocompartmental first-order kinetics model, regulated by two rates, and accounting for real elimination as well as binding of PFOS to non-exchangeable structures. Elimination was more rapid in rabbits, with a pseudo first-order dissipation half-life of 88 days compared to the 230 days observed for chickens. By contrast, the calculated assimilation efficiency for rabbits was almost 1, very close to full absorption, significantly higher than the 0.66 with confidence intervals of 0.64 and 0.68 observed for chickens. The results confirm a very different kinetics than that observed in single-dose experiments confirming clear dose-related differences in apparent elimination rates in rabbits, as previously described for humans and other mammals; suggesting the role of a capacity-limited saturable process resulting in different kinetic behaviours for PFOS in high dose versus environmentally relevant low dose exposure conditions. The model calculations confirmed that the measured maximum concentrations were still far from the steady state situation, and that the different kinetics between birds and mammals should may play a significant role in the biomagnifications assessment and potential exposure for humans and predators. For the same dose regime, the steady state concentration was estimated at about 36μg PFOS/L serum for rabbits, slightly above one-half of the 65μg PFOS/L serum estimated for chickens. The toxicokinetic parameters presented here can be used for higher-tier bioaccumulation estimations of PFOS in rabbits and chickens as starting point for human health exposure assessments and as surrogate values for modeling PFOS kinetics in wild mammals and bird in exposure assessment of predatory species.
authors.affiliation: Laboratory for Ecotoxicology, INIA, Madrid, Spain.
authors.forename: J V
authors.initials: JV
authors.lastname: Tarazona
authors.affiliation: Toxicology and Pharmacology Department, Veterinary Faculty, UCM, Madrid, Spain. Electronic address: rodfermc@vet.ucm.es.
authors.forename: C
authors.initials: C
authors.lastname: Rodríguez
authors.affiliation: Laboratory for Ecotoxicology, INIA, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Alonso
authors.affiliation: Department of Instrumental Analysis and Environmental Chemistry, Institute of Organic Chemistry, Spanish National Research Council (IQOG-CSIC), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sáez
authors.affiliation: Toxicology and Pharmacology Department, Veterinary Faculty, UCM, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: González
authors.affiliation: Toxicology and Pharmacology Department, Veterinary Faculty, UCM, Madrid, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: San Andrés
authors.affiliation: Department of Instrumental Analysis and Environmental Chemistry, Institute of Organic Chemistry, Spanish National Research Council (IQOG-CSIC), Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Jiménez
authors.affiliation: Toxicology and Pharmacology Department, Veterinary Faculty, UCM, Madrid, Spain.
authors.forename: M I
authors.initials: MI
authors.lastname: San Andrés
mesh_terms: D017738:Alkanesulfonic Acids / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D001717:Birds / Q000378:metabolism*; D001835:Body Weight; D002645:Chickens / Q000378:metabolism; D004777:Environment; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D006207:Half-Life; D008322:Mammals / Q000378:metabolism*; D015233:Models, Statistical; D011817:Rabbits; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; C076994:perfluorooctane sulfonic acid
keywords: Comparison mammals and birds; Elimination half-life; PFOS; Rabbits; Toxicokinetics