Metabolism And Residue Depletion Of 8-2 Ftoh In Swine And Chicken

Perfluoroalkyl acids(PFAAs)have a wide range of applications in the industry,home and other fields,due to their excellent and unique hydrophilic and lipophilic properties.They are very persistent in the environment because of high chemical stability and solubility.And they are bioaccumulative and toxic.It has been reported that a series of PFAAs residues such as perfluorooctanoic acid(PFOA)and PFOS are detected in human blood,and there are also reports of residues of PFAAs in the human liver,indicating that PFAAs are common pollutants that may be related to human health.Perfluorooctanoic acid is associated with hypercholesterolemia,ulcerative colitis,thyroid disease,preeclampsia,cancerous kidney and testis.Studies have shown that rats can biotransform polyfluorinated alkyl phosphodiesters,fluorotelomer alcohols,and other perfluorinated precursors into PFAAs.The importance of PFAAs precursors for human exposure to PFAAs become apparent.8-2 fluorotelomer alcohol(8-2 FTOH)attracted the attention of scientists because of its maximum production capacity and proved to be a precursor of PFOA.It is known that the metabolites perfluoroalkyl carboxylic acid of 8-2 FTOH is biomagnified in the food chain and is absorbed and concentrated in plant tissues,animal tissues,eggs and milk.So humans are exposed to 8-2 FTOH through various routes,such as inhalation of dust,drinking water,and food consumption(including breast milk,fish,seafood,meat,and meat products).The plants used as feed have been shown to absorb perfluorocarboxylic acids from the soil and accumulate in vegetative organs and storage organs.Livestock are exposed through drinking water and animal feed.Therefore animal derived foods are a potential source of human exposure.In order to determine the extent of 8-2 FTOH metabolism to PFOA in food-animals and determine the toxicological effects of metabolites,it is necessary to study the metabolism and residue elimination of 8-2 FTOH in swine and chicken.Based on previous reports,this project established a liquid-liquid mass spectrometry method for the identification of metabolites in excreta,established a quantitative method for the determination of 8-2 FTOH and its metabolites in animal samples.The established method was used to study the metabolism and residue depletion of 8-2 FTOH in swine and chicken.1 Establishment of Quantitative Methods for 8-2 FTOH and its metabolites in Swine and Chicken samplesIn this study,the research subjects were 8-2 FTOH and its metabolites perfluoropentanoic acid(PFPe A),perfluorohexanoic acid(PFHx A),perfluoroheptanoic acid(PFHp A),PFOA,perfluorononanoic acid(PFNA),and 8-2 fluorotelomer carboxylate(8-2 FTCA),8-2 fluorotelomer unsaturated carboxylate(8-2 FTUCA),and 7-3 fluorotelomer carboxylate(7-3FTCA).The dispersive solid-phase extraction combined with LC-MS/MS was established to determine the concentration of compounds in animal samples.Through the optimization of the pretreatment conditions,the sample was extracted with acetonitrile,the adsorbent C18,PSA,and GCB were used to purify the impurities.The supernatant was blown to 0.5 m L and mixed with the equal volume of initial mobile phase and analysted by LC-MS/MS.The mobile phase consisted of 5 mmol/L ammonium acetate and methanol.The Poroshell EC-C18 column was used for multi-reaction monitoring under negative ion mode.The ion source temperature was 200°C,and 9 compounds separated well within 17 minutes.The limit of quantification of PFPe A,PFHx A,PFHp A,PFOA,and PFNA was 0.3 ?g/kg in all swine and chicken samples(excreta,plasma,liver,kidney,muscle,fat,heart,lung,stomach,large intestine,and small intestine),the limit of detection was 0.1 ?g/kg.The limit of quantification of 8-2 FTCA,8-2 FTUCA,and 7-3 FTCA were 0.5 ?g/kg in all swine and chicken samples,and the limit of detection was 0.15 ?g/kg.The limit of quantification of 8-2 FTOH were 5 ?g/kg in all swine and chicken samples,and the limit of detection was 1.5 ?g/kg.After the methodological assessment,all compounds were found in all swine and chicken samples.The average recoveries was more than 70%,and the inter-day coefficient of variation was less than 12%.2 Metabolism of 8-2 FTOH in Swine and ChickenIn this project,LC/MS-Q-TOF was used to identify 8-2 FTOH and its metabolites in swine and chicken excreta.LC-MS/MS was used to quantitatively determine the target compounds in excreta.The project was to determine the metabolic mode of 8-2 FTOH.The single dose of 8-2 FTOH for healthy three-way crossbred swine and 28-day Colibac was 125 mg/kg.b.w.,and excreta were collected after 6 h,12 h,24 h,and every 24 h interval until 168 h.The results showed that the recoveries of compounds in swine and chicken excreta within 7 days were 81.5% and 80.4%,respectively.The recoveries in swine feces and urine were 77.3% and 4.2%,respectively.The main compound in swine and chicken excreta was 8-2 FTOH.Based on the comparison of molecular weight,mass spectrometry,and the rules of compound metabolism,the 8-2 FTOH glucuronide conjugate and 8-2 FTOH sulfate conjugate reported in the literature were detected.The eight metabolites were controlled by the standards.This shows that the metabolism of 8-2 FTOH is consistent with different animal species.3 Residue Depletion of 8-2 FTOH in Swine and ChickenThe 8-2 FTOH was given to the swine and chicken for 7 d consecutively.The dose was 5 mg/kg.b.w..The animals were slaughtered at 6 h,1 d,3 d,7 d,14 d,and 21 d after stopping the exposure.The liver,kidney,muscle,fat,heart,lung,stomach,large intestine and small intestine were taken and stored at-20?.The target compounds in the tissues were quantified according to the above-mentioned method.The distribution rule of 8-2 FTOH in the two animals was analyzed to determine the tissues of longer remaining time.The result is as follows:Swine: After stopping the exposure of 8-2 FTOH,PFNA was not detected in all tissues of swine at all time points.At the withdrawal time of 21 d,PFHp A,PFOA,and 7-3 FTCA were still detected in the liver and kidney,and other tissues could detect PFHp A and PFOA.The elimination half-lives of PFHp A,PFOA,7-3 FTCA in swine liver were 9.2 d,16.1 d,and 6.5 d respectively.The elimination half-lives in swine kidney were 12.8 d,23.9 d,and 8.6 d respectively.Chicken: After stopping the exposure of 8-2 FTOH,PFOA,PFNA,and 7-3 FTCA were detectable in all tissues of the chicken at the withdrawal time of 21 d,but the tissues of the higher concentrations were liver and kidney.The elimination half-lives of PFOA,PFNA and 7-3 FTCA in chicken liver were 3.7 d,17.3 d,and 7.0 d respectively.The elimination half-lives in chicken kidney were 4.2 d,22.4 d,and 5.5 d respectively.PFPe A,PFHx A,PFHp A,8-2 FTCA,and 8-2 FTUCA in chicken tissues were present at a shorter time than swine,indicating that 8-2 FTOH metabolism in chicken was faster than swine.In summary,this project for the first time established a dispersive solid-phase extraction method for the detection of 8-2 FTOH and its metabolites in animal samples,and obtained metabolic pathways and material balance of 8-2 FTOH in swine and chicken.It elucidated the metabolic rules and species characteristics,It systematically elucidated the residue elimination of 8-2 FTOH in swine and chicken.The results of this project provide new reference information for the observation of the toxicological effects of 8-2 FTOH,filling the research gap of 8-2 FTOH in food animals.