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

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 (R) 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 mu g/L) in the urine and low levels of metabolites, whereas high roughage had at slaughter higher levels of metabolites than low roughage. Pracetam (R) treated animals showed high levels 4-acetaminophen (up to 130.000 mu g/L) and metabolites during treatment, and lower levels (2800 mu g/L) at slaughter. In the paracetamol treated animals 4-acetaminophen and metabolites were detectable during treatment (up to 130.000 mu g/L) and until 7 days after treatment (110 mu g/L). 4-Acetaminophen and metabolites were only present in tissues of treated animals, during treatment (11-14.800 mu g/L) and a few days after treatment (7-55 mu g/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.