Urinary excretion of the ß-adrenergic feed additives ractopamine and zilpaterol in breast and lung cancer patients

Authors: CHENG, TING-YUAN - Roswell Park Cancer Institute; Shelver, Weilin; HONG, CHI-CHEN - Roswell Park Cancer Institute; MCCANN, SUSAN - Roswell Park Cancer Institute; DAVIS, WARREN - Roswell Park Cancer Institute; ZHANG, YALI - Roswell Park Cancer Institute; AMBROSONE, CHRISTINE - Roswell Park Cancer Institute; Smith, David

Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/16/2016
Publication Date: 10/12/2016
Publication URL: https://handle.nal.usda.gov/10113/5509863
Citation: Cheng, T.D., Shelver, W.L., Hong, C., McCann, S.E., Davis, W., Zhang, Y., Ambrosone, C.B., Smith, D.J. 2016. Urinary excretion of the ß-adrenergic feed additives ractopamine and zilpaterol in breast and lung cancer patients. Journal of Agricultural and Food Chemistry. 64(40):7632-7639.

Interpretive Summary: Ractopamine and zilpaterol are two ß-agonists that received approval by the U.S. Food and Drug Administration (FDA) for use as livestock feed additives. Human exposure to residues of approved ß-agonists is expected in countries for which approvals exist, but no published research has assessed exposure levels in these countries. We evaluated human exposures to ractopamine and zilpaterol residues by quantifying each ß-agonist in pre-surgical urine samples collected from a group of breast and lung cancer patients with data on usual meat intake. In addition, we examined whether the detectable concentrations of the ß-agonist were associated with meat intake levels. We hypothesized that individuals with higher levels of meat intake, including red meat and poultry, were more likely to have detectable urinary concentrations of the ß-agonists used as feed additives than those with lower levels of meat intake. However, we did not observe a clear relationship between urinary concentrations of ß-agonists and estimated average daily meat consumption. We observed low detection rates and even lower rates of quantifiable residues broadly support the procedures used by the US FDA Center for Veterinary Medicine to establish maximum residue levels in food animals. That is, the US regulatory framework seems –at least in the case of ß-agonists– to be successful in minimizing exposures to residue.

Technical Abstract: Background: ß-agonists have been legally used in the U.S. for almost two decades to increase lean muscle mass in meat animals. Despite a cardiotoxic effect after high-dose exposure, there has been limited research on human ß-agonist exposures related to meat consumption. Objectives: We quantified urinary concentrations of ractopamine and zilpaterol, two FDA-approved ß-agonist feed additives, and examined the extent to which the concentrations were associated with estimated usual meat intake levels. Methods: Overnight urine samples from 324 newly diagnosed breast cancer patients and spot urine samples from 46 lung cancer patients at the time of diagnosis, prior to treatment, were collected during 2006-2010 and 2014-2015, respectively. Urinary ractopamine and zilpaterol concentrations were measured by LC-MS/MS. Average daily meat intake during the previous year was estimated from a food frequency questionnaire. Results: The estimated total meat intake amount was 80.5 ± 47.4 g/day (mean ± standard deviation) in breast cancer patients and 76.9 ± 53.1 g/day in the lung cancer patients. Ractopamine and zilpaterol, respectively, were detected in 8.1% and 3.0% of the urine samples collected (n = 370). Only 1.1% (n=4) of the urine samples had zilpaterol concentrations above the limit of quantification, with the mean value of 0.07 ng/mL in urine. The presence of detectable ractopamine and zilpaterol levels were not associated with meat consumption (P>0.05 for total meat, red meat [unprocessed and processed], and poultry intake). Conclusions: In these two groups of cancer patients, the amount of meat-related exposure of ß-agonists was low.