The exogenous administration of commercial doses of sometribove to dairy cows does not produce significantly elevated residues of sometribove in meat due to its susceptibility to enzymatic degradation (Table 7.3). Sometribove was formulated in vegetable oil for subcutaneous injection so that it could be protected long enough from enzymatic degradation in tissues to provide sustained release over a two-week period between injections. Administration of 500 mg sometribove to dairy cows every two weeks is approximately equivalent to an average daily dose of 36 mg/cow, or 0.07 mg/kg (assumes 500-kg cow body weight). This level of exposure is approximately six times the estimated daily output of bST from the bovine pituitary81 and results in 2- to 10-fold increases in baseline concentrations of bST in blood. However, the absolute increases are within peak physiological bST levels observed in untreated cattle as blood bST levels fluctuate during the day.82
Exogenous administration of sometribove to dairy cows mimics the situation in high-producing dairy cows that have increased blood bST levels compared to lower-milk-producing cows.83,84 Although blood levels of bST (the radioimmunoassay used for sometribove detection cannot differentiate between bST and sometribove) are increased following sometribove administration, there is only a two-fold increase in residual bST levels (20 ng/g) in liver and no increases in muscle tissues (2.7 ng/g) of dairy cows (Table 7.3). When the potential exposure to sometribove from ingestion of 500 g of uncooked dairy cow meat by a 60-kg adult is compared to the highest gavage dosage (50 mg/kg/day) of sometribove (which produced no adverse effects in rats in a 13-week gavage study), the safety margin is at least 2 million-fold when comparing rat oral exposure to what humans might consume.76 Uncooked meat was used as a worst-case example in the calculated safety margin since cooking meat would denature bST.75
Pasteurization also denatures bST in milk.39 bST receptors that could facilitate the entry of bST into milk have not been identified on the bovine mammary gland by conventional binding assays.85 A level of 3 ng/ml of bST represents less than 0.00001% of the total protein in milk.86 Exogenous administration of 15-100 mg recombinant or pituitary bST/cow/day or 500 mg sometribove/cow/14 days does not increase the amount of bST in milk above endogenous levels of 0-10 ng/ml found in the milk of dairy cows.74,75,82,87-90 Only when greatly exaggerated doses (3000 mg/2 weeks) of sometribove were administered91 or 430 mg/cow/day for 21 days92 was it possible to detect a small increase of bST levels (~3 ng/ml) in milk.
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