Location: Food Animal Metabolism Research
2018 Annual Report
Objectives
Objective 1: Develop and/or validate rapid screening assays for the detection of environmental chemicals relevant to U.S. food production.
Sub-objective 1.A: Development of immunochemically based rapid screening methods for new and emerging persistent organic pollutants.
Sub-objective 1.B: Development of immunochemical purification methods for new and emerging persistent organic pollutants.
Objective 2: Determine levels and sources of dioxins and related compounds in the domestic food supply. Provide food safety agencies with data to confirm or refute the wholesomeness and competitiveness of beef, pork, chickens, turkeys and/or catfish.
Sub-objective 2.A: Conduct a nationally-based survey of PCDD/PCDF/PCB/PBDE levels in the domestic meat supply (beef, pork, chicken, turkey, and/or catfish) by collection of adipose tissues from U.S. slaughter facilities.
Sub-objective 2.B: Identify potential production-based or environmental sources of PCDDs/PCDFs/PCBs/PBDEs in food-producing animals.
Objective 3: Determine the uptake, metabolism (in vitro or in vivo), distribution, excretion, and fate of environmental contaminants with the goal of developing pharmacokinetic rate and volume constants pertinent to residue depletion, selection of marker compounds, and calculation of withdrawal intervals.
Sub-objective 3.A: Characterize the absorption, disposition, metabolism, and excretion (ADME) of POPs in food animals.
Sub-objective 3.B: Identify cellular fractions and enzyme classes responsible for the metabolism and putative dehalogenation of POPs.
Sub-objective 3.C: Characterize the bioavailability of POPs in animal systems from major exposure routes.
Sub-objective 3.D: Determine the fate and transport of POPs through soil during ambient weather conditions.
Sub-objective 3.E: Determine the effect of milk processing on POP concentrations in finished products.
Approach
Ubiquitous environmental contaminants enter the human meat supply when animals are exposed through surroundings and feeds. These compounds, known as persistent organic pollutants (POPs) satisfy the standards for chemicals of concern in that they are persistent, bioaccumulative, globally transported, and toxic. U.S. and international health organizations recommend continuing to decrease human exposure by lowering levels in foods and the environment. Our research efforts focus on reducing animal and human exposures to these contaminants using three approaches. First, we will develop rapid, inexpensive assays and cleanup tools for isolating and detecting POPs in food products. These assays could result in broad monitoring of the food supply, which currently is not feasible due to the high analysis costs. Second, we will continue to survey the U.S. meat supply (beef, pork, chicken, turkey and/or catfish) for POPs, and will track current levels with trends measured over the last two decades. These data are critical to regulatory agencies for risk assessment, and have revealed POP sources that have contributed to livestock exposures and contamination. Once identified sources of contamination may be eliminated or avoided. Third, we will perform basic research to determine pharmacokinetic parameters for POPs in laboratory and farm animals and will develop potential remediation methods using animal feeding studies. We will use these data to calculate withdrawal intervals, and elucidate strategies to decrease contaminant levels in food animals.
Progress Report
Objective 1A. 2-ethylhexyl-2,3,4,5 tetrabromobenzoate (TBB) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) haptens have been synthesized, conjugated to proteins to produce coating antigens and immunogens. The rabbit immunizations are completed, antibodies have been collected, and the titers for sensitivity are being performed.
Objective 2B. Two turkey producer associations across the Midwest have pledged support for a study to analyze for polybrominated diphenyl ethers. However, time commitments have prevented initiation of study/sampling protocols to be developed yet.
Objective 3A1. Due to difficulty in synthesizing this highly toxic compound, research effort was directed toward chemical relatives, i.e., mixed bromo/chloro-dioxins which are produced by the same pathways as the toxic chloro-dioxins, but whose pharmacokinetics have not been determined.
Objective 3A2. Absorption, distribution, metaoblism and excretion research in food animals was diverted to three related persistent organic pollutants, namely brominated diphenyl ethers in laying chickens. The ADME studies are completed and animal tissues are being processed and analyzed.
Objective 3B. Microsomal and S9 fractions have been isolated from dairy cows. However, characterization methods and experimental procedures have not been validated for the in vitro metabolism assays.
Objective 3C2. The hexabromocyclododecane (HBCD)/TBB/TBPH bioavailability study with incurred feed has been completed in rats, and animal tissues are being processed and analyzed.
Objective 3E. The entire study with 12 persistent organic pollutants was performed, completed, and the manuscript has been submitted to the journal.
Accomplishments
1. Persistent organic pollutant distribution during milk processing. Milk is a complex food that is often processed into foods such as skim milk, creams, cheeses, and/or whey-based products. During processing, trace-level chemical contaminants might become concentrated in such products depending upon the chemical characteristics of the contaminant. ARS scientists in Fargo, North Dakota determined how 12 common persistent organic pollutants with known chemical properties partitioned into milk fractions used for the production of human foods. The fat solubility of an individual chemical was reasonably predictive of its partitioning into various milk fractions. Collectively, data on the fate of chemicals during milk processing will allow the development of useful predictive models if a contamination event occurs.
2. Bioavailability of brominated flame retardants. Brominated flame retardants (BFRs) are commonly applied to consumer products to reduce the risk of fires. However, some BFRs are believed to be toxic and are of human health concern because humans are exposed to BFRS from a variety of sources and they could be absorbed in the gut. A major route of exposure to BFRs, especially in children, is through the consumption of household dust. Agricultural Research Service scientists in Fargo, North Dakota measured the levels of three major BFRs in household dust, fed the dust to rats, and measured the appearance of each BFR in rat tissues. The researchers learned that each BFR was readily absorbed from household dust and that each preferentially accumulated in fat tissue. These results will be used by risk assessors when predicting the overall hazards to humans of BFRs from all sources.
Review Publications
Hakk, H., Sikora, L.S., Casey, F.X. 2018. Fate of estrone in laboratory-scale constructed wetlands. Ecological Engineering. 111:60-68. https://doi.org/10.1016/j.ecoleng.2017.11.005.
Sanchis, A., Salvador, J.P., Campbell, K., Elliott, C.T., Shelver, W.L., Li, Q.X., Marco, M.P. 2018. Fluorescent microarray for multiplexed quantification of environmental contaminants in seawater samples. Talanta. 184:499-506. https://doi.org/10.1016/j.talanta.2018.03.036.
Lupton, S.J., Shappell, N.W., Shelver, W.L., Hakk, H. 2018. Distribution of spiked drugs between milk fat, skim milk, whey, curd, and milk protein fractions: Expansion of partitioning models. Journal of Agricultural and Food Chemistry. 66(1):306-314. https://doi.org/10.1021/acs.jafc.7b04463.
Singh, A., Hakk, H., Lupton, S.J. 2018. Facile synthesis of high specific activity 4-[1-14C]butyl-1,2-diphenylpyrazolidine-3,5-dione (phenylbutazone) using nucleophilic substitution. Journal of Labelled Compounds and Radiopharmaceuticals. 61(4):386-390. https://doi.org/10.1002/jlcr.3597.
Shelver, W.L., Lupton, S.J., Shappell, N.W., Smith, D.J., Hakk, H. 2018. Distribution of chemical residues among fat, skim, curd, whey, and protein fractions in fortified, pasteurized milk. ACS Omega. 3(8):8697-8708. https://doi.org/10.1021/acsomega.8b00762.
