| Recently melamine was found to have contaminated the feed of multiple food production species leading to concern over the ability to establish an appropriate withdrawal interval and protect the safety of the food supply.The objective of this study was to assessment of melamine toxicity in piglets,and to develop a model for estimating appropriate plasma withdrawal intervals after exposure to melamine contaminated feed under a longer time.Experiment 1 Toxic Effects of Diet Supplementation Melamine on Weaned PigletsTwenty Duroe×Landrace×Yorkshire weaned piglets of weighing(5.87±0.95)kg were randomly allocated to 4 treatments to investigate the effects of melamine on growth performance,nutrient digestibility,tissue residue,and function of kidney.The 4 treatments were fed respectively with basal diet and basal diet supplemented with 100,500 and 1000 mg/kg melamine.The trial lasted for 42 d.Piglets were weighted and blood samples were collected from precaval vein on every weekend,to analyze the concentration of CysC, CRE,SUN and melamine,and the activities of GPT and GOT.At the end of trail,all of piglets were slaughted to examine the pH value of gastrointestinal contents,to observe the pathological change of kidney and the residue levels in the kidney,muscle and liver. Results showed that with the increasing of melamine supplementation levels,ADG (P<0.05),crude protein(P<0.01),calcium(P<0.01)and phosphorus(P<0.01)digestibility were decreased linearly and quadraticly,the contents pH value of stomach and duodenum were increased linearly and quadraticly(P<0.01).There were no significant difference on serum GOT activity and SUN levels,but serum GPT(P<0.05) reduced linearly and quadraticly.The melamine residue levels of kidney,muscle,liver and serum increased linearly and quadraticly with the supplements of melamine(P<0.01).The correlations between melamine addition contents and residue levels in kidney,muscle,liver and plasma of weaned piglets were 0.956,0.98,0.927 and 0.917 respectively and established quadratic regression equation.The correlations between residue level in plasma and residue levels in kidney,muscle and liver of weaned piglets were 0.858,0.92 and 0.952 respectively and established quadratic regression equation.The serum CRE(P<0.01) and CysC(P<0.01) increased linearly and quadraticly with the supplements of melamine.The extent of damage of kidney cortex and medulla were increased with the supplements of melamine.It was indicated that melamine inhibited the growth and damaged the kidney of piglets,and with the increasing of melamine supplementation levels,the melamine residue levels of kidney,liver and plasma and the toxic effects enhanced.Experiment 2 Research of Melamine Blood Disappearance Prediction Model in Weaned PigletsAt the end of feeding trial,piglets in experiment 1 were fed 200 g diet supplemented with melamine,following weighted and sampled blood.Then plasma samples were collected at 0 h,1 h,2 h,4 h,8 h,12 h and 24 h,extracted for melamine and analyzed. Based on the plasma melamine concentration at different time points,linear,quadratic and exponential clearance predicted models were established for different treatments. According to the significant,correlation and residuals of the dynamic elimination models, exponential models were the optimal dynamic elimination models.The models could better predicted plasma concentration.Correlation between predicted and observed values were 0.972(P<0.01),0.926(P<0.01),and 0.839(P<0.01) for 100mg/kg,500mg/kg and 1000mg/kg treatments respectively.The porcine plasma melamine dynamic elimination models estimated the half-life of melamine in the plasma were 6.53 h,6.02h and 6.51 h, the withdrawal interval(based on plasma residues<50μg/mL) of 29.46 h,40.07 h and 49.6 h respectively.After 38.09 h,48.03 h and 58.21 h,the plasma contaminant concentration could lower than the detectability level of 20μg/mL.The results indicated that exponential models revealed good accuracy and precision at terminal time points (most important for withdrawal interval prediction).The half-life of plasma melamine was very close to 6 to 6.5 h and an average of 6.35 h.But the withdrawal intervals,based on plasma residues<50μg/mL or<20μg/mL,were different among the three treatments,and increased with the supplements of melamine. |