RESUMO

Poultry production is linked to veterinary drug use to treat diseases. Few ectoparasitic compounds are approved for poultry. Fipronil is a pesticide widely used in agriculture. It is also a drug authorized to control ectoparasites in small animals and, in some countries, in cattle. There has been evidence of fipronil extra-label use in laying hens, mainly to control the red mite Dermanyssus gallinae. Fipronil's popularity is due to its high toxicity to invertebrates. It could be metabolized to more toxic metabolites that potentially damage human health. In the present study, we carry out a quantitative exposure assessment and risk characterization for fipronil residues in laying hen eggs for local consumption in five cities of Buenos Aires province in Argentina, namely, Azul, Balcarce, Juarez, Chaves, and Tandil. Consumption surveys and egg sampling were conducted for three summer periods. Eggs were analyzed by UFLC-MS-MS. Fipronil prevalence, residue concentrations, residue stability to cooking methods, egg consumption, among the most important variables were modeled. The results indicated that 20.7% of samples contained fipronil residues. The highest residue was fipronil sulfone metabolite. Fipronil concentrations quantified ranged between 10 and 2510 ppb (median value = 150 ppb). When eggs were cooked, fipronil residues were stable. The exposure assessment and risk characterization revealed that the highest probability of consuming eggs with fipronil residues above the admissible limits was for young adults (20.8%), followed by babies (16.9%), young children (16.4%), children (13.4%), teenagers (10.3%), older adults (9.41%), and adults (8.65%). These results suggest an unacceptable risk associated with egg consumption with fipronil residues for all age groups. PRACTICAL APPLICATION: Fipronil is widely used as an extra-label way on laying hens since its use is prohibited in poultry production both in Argentina and in most countries. This molecule has been classified as Class II, a moderately hazardous pesticide because it could damage various human organs. Fipronil residues in eggs could be one of the exposure pathways for consumers. Monitoring residual levels and carrying out the health risk assessment in eggs are thus in an urge.

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RESUMO

Drugs are used in veterinary medicine to prevent or treat animal diseases. When rationally administered to livestock following Good Veterinary Practices (GVP), they greatly contribute to improving the production of food of animal origin. Since humans can be exposed chronically to veterinary drugs through the diet, residues in food are evaluated for effects following chronic exposures. Parameters such as an acceptable daily intake (ADI), the no-observed-adverse-effect level (NOAEL), maximum residue limits (MRLs), and the withdrawal periods (WPs) are determined for each drug used in livestock. Drug residues in food exceeding the MRLs usually appear when failing the GVP application. Different factors related either to the treated animal or to the type of drug administration, and even the type of cooking can affect the level of residues in edible tissues. Residues above the MRLs can have a diverse negative impact, mainly on the consumer's health, and favor antimicrobial resistance (AMR). Drug residue monitoring programmes are crucial to ensure that prohibited or authorized substances do not exceed MRLs. This comprehensive review article addresses different aspects of drug residues in edible tissues produced as food for human consumption and provides relevant information contributing to rational pharmacotherapy in food-producing animals.

RESUMO

This experimental work reproduces the fipronil extra-label administration performed by producers in laying hens. The scientific goal was to characterize the residual concentrations in eggs from treated hens and suggest the withdrawal periods that should be respected to avoid risk for consumers. Thirty-four laying hens were allocated into two groups: Group A was treated with fipronil in feed, two single doses of 1 mg kg-1  day-1 ; Group B was administered a single dose of 1 mg kg-1 by the topical route. Fipronil egg residues were quantified by HPLC-MS/MS. Fipronil and its sulphone metabolite (fipronil-SO2 ) were measured in egg after both treatments. The highest egg residual profile was always for fipronil-SO2 . Mean maximum egg concentrations (Cmax ) of 228.5 ± 79.8 ng/g (fipronil) and 1,849 ± 867 ng/g (fipronil-SO2 ) were found after fipronil administration in feed. The lowest residual levels were quantified after the topical treatment with Cmax of 27.1 ± 4.9 and 163 ± 26 ng/g for fipronil and fipronil-SO2 . Mean fipronil marker residues and established MRLs allowed calculating the withdrawal periods, the shortest being 74 days after topical administration. Such a long withdrawal period is difficult to meet in egg production systems. Thus, the extra-label use of fipronil in laying hens should not be recommended under any circumstances.

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The available information on drug residue stability in chicken egg is scarce. The objective of this study was to evaluate the stability of drug residues in egg under different traditional cooking procedures. Fresh eggs were spiked with different drug concentrations of albendazole (ABZ) and its albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2) metabolites; flubendazole (FLBZ) and its reduced flubendazole (R-FLBZ) and hydrolyzed flubendazole (H-FLBZ) metabolites; amoxicillin (AMX); and enrofloxacin (EFX) and its ciprofloxacin (CFX) metabolite. The egg samples were cooked in different ways, namely, boiling, microwaving, and omelette making. Drug residue concentrations in egg were quantified by HPLC with UV or fluorescence detectors. ABZ and ABZSO concentrations in egg were not affected by boiling and microwaving, while the omelette processing significantly reduced these molecules. Residues of ABZSO2 in egg were stable or increased after all cooking procedures. In contrast, FLBZ and its metabolites FLBZ-H and FLBZ-R residues in egg decreased after all treatments. The residue concentration quantified for EFX and CFX did not show significant changes after any cooking method. AMX residues were unstable, with extremely significant drug reduction after all cooking processes. Conventional methods of egg cooking cannot be considered a tool to eliminate all veterinary drug residues.

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This work characterized the egg residual concentrations of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2 ) metabolites and evaluated their effect on egg fertility and hatchability after ABZ treatments to laying hens. Seventy hens were allocated in groups: Group-1 was the control without treatment; Group-2 received a single ABZ oral dose (10 mg/kg); Group-3, -4 and -5 were treated with ABZ in medicated feed over 7 days at 10, 40, or 80 mg kg-1  day-1 , respectively. Eggs were analyzed to determine the ABZ/metabolite level by HPLC or subjected to incubation to evaluate the fertility and hatchability. Only ABZSO and ABZSO2 metabolites were quantified in egg after ABZ single oral administration with maximum concentrations of 0.47 ± 0.08 and 0.30 ± 0.07 µg/ml, respectively. ABZ and its metabolites were found in eggs after 7-day ABZ treatments. The egg residue exposure estimated as AUCs (areas under the concentration vs. time curve) were 100.5 (ABZ), 56.3 (ABZSO) and 141.3 µg hr g-1 (ABZSO2 ). ABZ administration did not affect the egg fertility at any dosages. Egg hatchability was not affected by ABZ treatment at 10 mg/kg in medicated feed, but it decreased when the dose was 4-8 times higher. These results should be considered when ABZ is used for deworming laying hens.

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The goals were to determine the ivermectin (IVM) plasma pharmacokinetics, tissue and egg residue profiles, and in vitro metabolism in laying hens. Experiments conducted were (1) 8 hens were intravenously treated with IVM and blood samples taken; (2) 88 hens were treated with IVM administered daily in water (5 days) (40 were kept and their daily eggs collected; 48 were sacrificed in groups (n = 8) at different times and tissue samples taken and analyzed); (3) IVM biotransformation was studied in liver microsomes. Pharmacokinetic parameters were AUC = 85.1 ng·day/mL, Vdss = 4.43 L/kg, and T1/2el = 1.73 days. Low IVM tissue residues were quantified with the highest measured in liver and skin+fat. IVM residues were not found in egg white, but significant amounts were quantified in yolk. Residues measured in eggs were greater than some MRL values, suggesting that a withdrawal period would be necessary for eggs after IVM use in laying hens.

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