The Synthesis and Applications of lsotopically Labelled Compounds 561

ROLE OF LABELLED COMPOUNDS IN STUDIES OF THE FATE OF AGROCHEMICALS

Ralph O. Mumma

Department of Entomology, Pennsylvania State University, University park,

PA 16802

In order to use an agrochemlcal in most countries, it must first be registered in that country. Usually this registration requires the company marketing the chemical to submit environmental fate data. These studies may involve the fate of the chemical in plants, animals, soils, water and alr, and routinely use radlolabelled agrochemicals. Examples of typical studies will be cited emphasizing the characteristics of the experiment, the positions and type of radlolabel used, and the implications of the data obtained from the experiments. Since agrochemicals are usually biologically active, it is a common practice to study the effect of the agrochemlcal on some property of the soil, plant or animal. In these cases radiolabelled substrates other than the agrochemical are used and the fate of the substrates studied. Radlolabelled experiments with plant callus and suspension cultures have contributed greatly to our knowledge of the fate of agrochemlcals in plants and these studies have influenced the development of species specific agrochemicals.

THE USE OF LABELLED COMPOUNDS IN STUDIES OF BIOACCUMULATION OF POLLUTANTS IN ECOSYSTEMS. C.H. Walker, Department of Physiology & Biochemistry, University of Reading, P.O.1~ox 228, Whiteknights, Reading RG6 2AJ, U.K.

The metabolic fate of ~C labelled organochlorine insecticides has been studied in vivo in pigeon (Columba l i v i a ) , Japanese quail (Corturnix

T~ ~ormorant (Phalacrocorax carbo), rat and rabbit, to aid ing of the reasons for their bioacucumulation in ecosystems. The

enzymic processes responsible for biotransformation have been investigated I~ parallel in vi tro studies using l i ver homogenates and microsomes. ~C pp'DDT w ~ o l i s e d very slowly in pigeon and quail. In pigeon,

polar metabolites were excreted exceptionally slowly and most of the ~"C dose was retained in the tissues as p~DDE 11 weeks after ~ssingle dose. Male rats were given single doses of ~"C HEOD (dieldr in), ~C HCE (1,2,3,4,9,9-hexachloro;~,4,4a,5,6,7,8,8a octahydro exo-7,9 epoxy-l,4 methanonaphthalene) or ~C HEOM (1,2,3,4,9,9-hexachloro-1,4,4a,5,6,7,8,8a octahydro exo 6,7 epoxy-l,4 methanonaphthalene). HCE and HEOM were rapidly metabolised in vitro and in vivo and metabolites rapidly excreted in bi le. liCE was also~ap- ' i~meta~-o- l~ by pigeon, Japanese quail and rabbit. HEOD was slowly metabolised and the metabolites slowly excreted. Cormorants had:- (1) lower act iv i t ies of l i ve r enzyme than rats, and (2) considerably longer dieldrin half lives than rats. I t was concluded that the tendency for organnchlorine compounds such as dieldrin and pp'DDE to bioaccumulate is a consequence of slow rates of metabolism. The biodegradable dieldrin analogues HCE and HEOM were relat ively non-persistent.

FOLLOWING MACROMOLECULAR INTERACTIONS AND SUGAR METABOLISM USING SITE SPECIFIC 3H LABELLING AND 3H NMR SPECTROSCOPY.

Philip Williams, Melvin Klein, Sun Un, Hiromi Morimoto, Kalle Gehring and David Wemmer.

National Tritium Labeling Facility and Chemical Biodynamics Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720, U.S.A.

Although there has been extensive use of 3H as a tracer in many different studies of metabolism, and also in studies of solvent exchange in macromolecules, there has been relatively little use of the advantageous characteristics of 3H for following such processes with high resolution NMR. Since 3H has a spin of 1/2 (giving relaxation characteristics and chemical shifts essentially identical to a proton), a high gyromagnetic ratio (giving high sensitivity), and no natural abundance background, it is ideal for NMR studies when combined with high specific activity labelling. We will discuss several examples of this combined approach. First, we have studied the binding of maltose, and oligomers of maltose, to the maltose transport protein from E. coll. Selective labelling of the sugar allowed us to characterize its bound state, and use of saturation transfer allowed us to follow the exchange of sugar between bound and free forms as a function of temperature. This general approach has also been used in vivo to follow the metabolism of glucose by intact red blood cells. It was possible to follow both the main metabolic path, including the concentration of the substrate glucose and the product lactate as a function of time, and also to detect intermediates along the glycolysis pathway. Appearance of a 3H signal in the solvent indicated that a secondary parallel pathway was also active. With the combination of modern methods for labelling with high specific activity and high sensitivity NMR spectrometers we expect to see many applications of this methodology in the future.