4-acetaminophen (Paracetamol) levels in treated and untreated veal calves, an update

• Published in: Food control Vol. 147; p. 109577
• Main Authors: Groot, M.J., van Dijk, A., van Baak, M.J., Boshuis, P., van de Braak, A.E., Zuidema, T., Sterk, S.S.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.05.2023
• ISSN: 0956-7135; 1873-7129
• DOI: 10.1016/j.foodcont.2022.109577

Recently, residues of 4-acetaminophen (paracetamol) have been found in urine of slaughter animals. To investigate its possible origin, a 7 week animal experiment was performed with 5 groups of 4 calves fed different amounts of roughage, and treated or not with 4-acetaminophen. Group 1 (control): new-born calves were fed, after the first days of colostrum, solely dairy based calf milk replacer (CMR). The animals from the other groups were 2–3 weeks of age at the start of the experiment and were fed the same CMR. Group 2 was administered oral Pracetam® 30 mg acetaminophen/kg Body Weight (BW) in the CMR, 5 days a week at alternate weeks, with maximum roughage. Group 3 was fed legal minimum roughage. Group 4 received the maximum roughage. Group 5 was administered human paracetamol pills 30 mg/kg BW once a week at weeks 2–6 with maximum roughage. The animals were housed in separate pens on slatted rubber floors without bedding. The controls were housed in a different room than the other animals. Urine was sampled once in the acclimatization period and for 5 days after treatment. At week 2, 4 and 6 at respectively 1, 2 and 3 days after treatment, one animal from groups 2 and 5 was sacrificed. An additional animal from group 4 was sacrificed at week 4, the rest of the animals at day 43. Urine, muscle, liver and kidney were analysed for residues of 4-acetaminophen and its metabolites. It appeared that controls and the low and high roughage animals had almost no 4-acetaminophen (<3 μg/L) in the urine and low levels of metabolites, whereas high roughage had at slaughter higher levels of metabolites than low roughage. Pracetam® treated animals showed high levels 4-acetaminophen (up to 130.000 μg/L) and metabolites during treatment, and lower levels (2800 μg/L) at slaughter. In the paracetamol treated animals 4-acetaminophen and metabolites were detectable during treatment (up to 130.000 μg/L) and until 7 days after treatment (110 μg/L). 4-Acetaminophen and metabolites were only present in tissues of treated animals, during treatment (11–14.800 μg/L) and a few days after treatment (7–55 μg/L). A striking effect was the decrease in concentration of 4-acetaminophen and metabolites in time during treatment in the tissues. Liver enzyme induction may provide a possible explanation for this. Urine•Controls and low roughage: almost no 4-acetaminophen in urine and low levels of metabolites•High roughage: low levels of 4-acetaminophen. At slaughter: levels of metabolites higher than low roughage•Pracetam®: 4-acetaminophen + metabolites during treatment, at slaughter. 3 days after last treatment low levels•Paracetamol: 4-acetaminophen + metabolites during treatment and until 7 days after treatment Tissues•Only 4-acetaminophen and metabolites present in tissues of treated animals, during treatment and a few days after stopping treatment•Levels of 4-acetaminophen and metabolites in tissues reduce in time during treatment, liver enzyme induction possible explanation Enzyme induction•(UGT) activity increased in 4-acetaminophen treated animals and was higher in high roughage animals as compared with low roughage animals