Discrimination between the exogenous and endogenous origin of thiouracil in farm animals, the final chapter?

Abstract

Thiouracil (2-thiouracil) is a thyreostatic compound that can be used as an illegal growth promoter. In bovine, porcine and other farm animals, low concentrations of thiouracil are detected in urine. There is much debate on which concentrations can be considered to originate from feed ('natural') and which concentrations are caused by the illegal administration of thiouracil for growth-promoting purposes. Currently, a threshold value of 10 µg/L in urine is applied. The threshold value is based on epidemiological data. Data on thiouracil from animals treated with thiouracil is scarce. We conducted a study whereby animals were fed with rapeseed, rapeseed with thiouracil, or regular feed with thiouracil (low and high concentration). It was determined that administration of thiouracil leads to concentrations higher than the current 10 µg/L threshold of thiouracil and its metabolites in urine during treatment. Animals fed with rapeseed showed higher thiouracil concentrations than the control group, mostly above 10 µg/L and in some cases above 30 µg/L. In the discovery study, several biomarkers for thiouracil treatment were tentatively identified and confirmed with reference standards. One metabolite was identified as indicative for thiouracil abuse, namely 6-methyl-thiouracil. Another metabolite, 4-thiouracil, was indicative for endogenous formation and did not increase during 2-thiouracil treatment. 6-Methyl-thiouracil was not found in urine samples from the Dutch routine control programmes that contained (endogenous) 2-thiouracil above the threshold value. However, 4-thiouracil was found at high concentrations in the same samples when 2-thiouracil was present. This study's overall conclusion is that the threshold value for thiouracil in bovine urine samples should be set at 10 µg/L and for porcine urine samples at 30 µg/L. Also, confirmation of 6-methylthiouracil and 4-thiouracil should be used as indicators for exogenous or endogenous origin in routine control monitoring programmes.

Pojavnost tiouracila u svinjećim i goveđim urinima prikupljenih na hrvatskim farmama

“…An animal receiving TU in the diet will retain more water and increase carcases weight. Meat produced from those animals will be of inferior quality, due to the high water content (Abuín et al, 2008;Vanden Bussche et al, 2012;Blokland et al, 2021).…”

“…Furthermore, according to Arrizabalaga-Larrañaga et al (2022), the markers 4-thiouracil and 6-methyl thiouracil should be analysed to distinguish between exogenous and endogenous TU. In the absence of 6-methyl-thiouracil and in the presence of 4-thiouracil, it can be concluded that TU is not originating from illegal treatment (Blokland et al, 2021) and rather can occur endogenously as a consequence of a diet containing cruciferous plants (rapeseed, rapeseed meal, broccoli, cauliflower) (Woźniak et al, 2012;Stark et al, 2014).…”