The residues of lignocaine in sheep

Summary

The purpose of this study was to evaluate the decline in lignocaine tissue residues following treatment of sheep at the highest likely dose level of 10 mg/kg with a commercially available injectable formulation of lignocaine (lignocaine hydrochloride 20 mg/mL). This study was conducted under Good Laboratory Practice (GLP) guidelines.

Twenty-five (25) crossbred sheep (15 males and 10 females) weighing 10.8-18.0kg and 3-6 weeks of age were purchased from a commercial sheep farm for enrolment into the study. Sheep were inspected to be in 'normal' health and had not received any treatment containing lignocaine in their lifetime. Sheep were individually identified with uniquely numbered ear tags, weighed and allocated to treatment groups.

Residue calculations were conducted to determine indicative Withholding Periods (WHP) according to the ACVM Registration Standard and Guidelines for Determination of a Withholding Period for Veterinary Medicines (39 ACVM 03/03) and using Microsoft EXCEL 2010 Version 14.0 in relation to lignocaine.As there was not a current (Australian) Maximum Residue Limit (MRL) for lignocaine in sheep tissue, the previous MRL of 20 μg/kg (0.02 mg/kg) (withdrawn in 2012) and the limit of quantitation (LOQ) (0.02 μg/kg) were used to provide indicative "probable" and "worst case" estimates of possible WHPs, with the latter potentially being more relevant to any future ESI.  The levels of 2,6-xylidine (DMA) were quantified such that a metabolism profile for the metabolite in each tissue could be defined.

Quantifiable levels of lignocaine and 2,6-xylidine were observed in all tissues. Residue calculations were performed for lignocaine in muscle, liver, kidney and fat and not for injection site, given the location (in the scrotal sack and tail stump, tissues subject to trimming during processing) and 'worst case' aspect as not being representative of standard edible tissue.  Group mean lignocaine residues in muscle, liver and kidney declined to < LOQ in all edible tissues by 14 days post-treatment.

Based on the previously withdrawn MRL for lignocaine in ovine tissues, the limiting tissue appeared to be fat, with an indicative WHP of 3 days when lignocaine was administered via subcutaneous injection to the scrotal neck and tail base of lambs at marking at a nominal dose level of 10 mg/kg. Similarly, if a future MRL or limiting concentration was based on the same figure as the method LOQ, fat would also be the limiting tissue, with an indicative WHP of 22 days.