RESIDUE REVIEWS VOLUME 35 RESIDUE REVIEWS Residues of Pesticides and Other Foreign Chemicals in Foods and Feeds RUCKST ANDS-BERICHTE Rtickstande von Pestiziden und anderen Fremdstoffen in N ahrungs- und Futtermitteln Editor FRANCIS A. GUNTHER Assistant Editor JANE DAVIES GUNTHER Riverside, California ADVISORY BOARD F. BAR, Berlin, Germany' F. BRO-RASMUSSEN, Copenhagen, Denmark J. W. COOK, Washington, D.C .• D. G. CROSBY, Davis, California S. DORMAL-VAN DEN BRUEL, Bruxelles, Belgium C. L. DUNN, Wilmington, Delaware • H. FREHSE, Leverkusen-Bayerwerk, Germany J. C. GAGE, Macclesfield, England • H. GEISSBUHLER, Basel, Switzerland S. A. HALL, Beltsville, Maryland' T. H. HARRIS, Bethesda, Maryland L. W. HAZLETON, Falls Church, Virginia' H. HURTIG, Ottawa, Canada O. R. KLIMMER, Bonn, Germany' G. K. KOHN, Richmond, California H. F. LINSKENS, Nijmegen, The Netherlands' H. MAIER-BoDE, Bonn, Germany N. N. l\fELNIKOV, Moscow, U.S.S.R .• R. MESTRES, Montpellier, France P. DE PIETRI-ToNELLI, Milano, Italy· R. TRUHAUT, Paris, France VOLUME 35 ,·,. t -• " ~ SPRINGER-VERLAG BERLIN • HEIDELBERG • NEW YORK 1971 All rights reserved. No part of this book may be translated or reproduced in any fonn without written pennission from Springer-Verlag. © 1971 by Springer-Verlag New York Inc. Library of Congress Catalog Card Number 62-18595. Softcover reprint of the hardcover 1s t edition 1971 The use of general descriptive names, trade names, trade marks, etc. in this publication, even if the fonner are not especially identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Marks Act, may accordingly be used freely by anyone. ISBN-13: 978-1-4612-9814-4 e-ISBN-13: 978-1-4612-9812-0 DOl: 10.1007/978-1-4612-9812-0 Preface That residues of pesticide and other "foreign" chemicals in food stuffs are of concern to everyone everywhere is amply attested by the reception accorded previous volumes of "Residue Reviews" and by the gratifying enthusiasm, sincerity, and efforts shown by all the in dividuals from whom manuscripts have been solicited. Despite much propaganda to the contrary, there can never be any serious question that pest-control chemicals and food-additive chemicals are essential to adequate food production, manufacture, marketing, and storage, yet without continuing surveillance and intelligent control some of those that persist in our foodstuffs could at times conceivably endanger the public health. Ensuring safety-in-use of these many chemicals is a dynamic challenge, for established ones are continually being dis placed by newly developed ones more acceptable to food tech nologists, pharmacologists, toxicologists, and changing pest-control requirements in progressive food-producing economies. These matters are of genuine concern to increasing numbers of governmental agencies and legislative bodies around the world, for some of these chemicals have resulted in a few mishaps from improper use. Adequate safety-in-use evaluations of any of these chemicals per sisting into our foodstuffs are not simple matters, and they incorporate the considered judgments of many individuals highly trained in a variety of complex biological, chemical, food technological, medical, pharmacological, and tOxicological diSCiplines. It is hoped that "Residue Reviews" will continue to serve as an integrating factor both in focusing attention upon those many residue matters requiring further attention and in collating for variously trained readers present knowledge in specific important areas of residue and related endeavors; no other single publication attempts to serve these broad purposes. The contents of this and previous volumes of "Residue Reviews" illustrate these objectives. Since manuscripts are published in the order in which they are received in final form, it may seem that some important aspects of residue analytical chemistry, biochemistry, human and animal medicine, legislation, pharmacology, physiology, regulation, and toxicology are being neglected; to the contrary, these apparent omissions are recognized, and some pertinent manuscripts are in preparation. However, the field is so large and the interests in it are so varied that the editors and the Advisory Board earnestly solicit suggestions of topics and authors to help make this international book series even more useful and informative. v vi Preface "Residue Reviews" attempts to provide concise, critical reviews of timely advances, philosophy, and Significant areas of accomplished or needed endeavor in the total field of residues of these chemicals in foods, in feeds, and in transformed food products. These reviews are either general or specific, but properly they may lie in the domains of analytical chemistry and its methodology, biochemistry, human and animal medicine, legislation, pharmacology, physiology, regulation, and toxicology; certain affairs in the realm of food technology con cerned specifically with pesticide and other food-additive problems are also appropriate subject matter. The justification for the prepara tion of any review for this book-series is that it deals with some aspect of the many real problems arising from the presence of residues of "foreign" chemicals in foodstuffs. Thus, manuscripts may encompass those matters, in any country, which 'are involved in allOwing pesticide and other plant-protecting chemicals to be used safely in producing, storing, and shipping crops. Added plant or animal pest-control chem icals or their metabolites that may persist into meat and other edible animal products (milk and milk products, eggs, etc.) are also residues and are within this scope. The so-called food additives (substances deliberately added to foods for flavor, odor, appearance, etc., as well as those inadvertently added during manufacture, packaging, distribu tion, storage, etc.) are also considered suitable review material. Manuscripts are normally contributed by invitation, and may be in English, French, or German. Preliminary communication with the editors is necessary before volunteered reviews are submitted in manu script form. Department of Entomology F.A.G. University of California Riverside, California December 7, 1970 Table of Contents Hygienic normalization of pesticide residues and their tolerance levels in foodstuffs in the U.S.S.R. By N. N. MELNIKOV and M. C. SHEVCHENKO . . . . 1 Materials in contact with foodstuffs: Technical and sanitary grounds in view of a general and specific legislation By A. SAMPAOLO .............. . 11 Pesticide legislation and residue problems in Portugal By A. M. S. SILVA FERNANDES ......... . 29 Pesticide regulation in South Africa By 1. H. WIESE and J. BOT. . . 49 Interaction between herbicides and soil microorganisms By D. R. CULLIMORE ............. . 65 Pesticide and growth regulator residues in pineapple By H. Y. YOUNG. . . . . . . . . . . . . . . . 81 Pesticides, pesticide residues, tolerances, and the law (U.S.A.) By ARTHUR BEVENUE and YOSHlHIKD KA WAND 103 Subject Index. . . . . . . . . . . . . . . . . . . . . . . 151 vii Hygienic normalization of pesticide residues and their tolerance levels in foodstuHs in the U.S.S.H. By N. N. MELNIKOV and M. C. SHEVCHENKO <) U Contents l. Introduction ..... 1 II. General outline of pesticide studies ..... 2 III. Tolerance levels of pesticides in foodstuffs ....... . 4 IV. Tolerance levels of pesticides in forage . . . . . . ................. . 5 V. Normalization of pesticide content in water reservoirs ... . ......... . 5 S~mma,ry ............... .......... ....... . 7 Resume.. . ...... . 8 Zusammenfassung . . . . . . . . . . .......... . 8 References ......................... . ........................ . 8 I. Introduction In the thirties, just after the mass application of pesticides for pests and plant disease control began, their application in the Soviet Union was regulated. The regulation applied not only to application conditions but to toxicant contents in foodstuffs as well; this regulation primarily concerned arsenic and fluorine compounds. As the assort ment of formulations and the scale of their usage in agriculture widened the methods of pesticide evaluations were improved and the conditions of their safe application were determined more accurately. After the second World War a well-founded scientific system of preventive measures has been developed in the USSR which makes it possible to preclude both direct and indirect effects of pesticides on man. The regulations on pesticide applications to control pests, plant diseases, and weeds are of the major importance in this system, as they provide safe conditions for labour and include measures pre venting the pesticide contamination of food, forage, and open water reservoirs. The system includes recommendations for treatment of All-Union Research Institute of Plant Protection Chemicals, Moscow Zh-88, <) U.S.S.R. .... Ministry of Public Health. 1 2 N. N. MELNIKOV and M. G. SHEVCHENKO growing plants and safety precautions on how to use the pesticide formulations, time of treating plants and animals (time before harvest or feeding), tolerance levels of pesticide residues in different products, etc. As new scientific data on a particular preparation are produced, the system of their application is also changed in order to exclude any possibility of harmful effects of pesticides on man. Strict hygienic regulation on tolerance levels of pesticide quantities in foodstuffs and systematic state control over their content within the country ensure full safety of human health from any possible long-time consequences of pesticide application. The regulations of pesticide application are worked out by the Ministry of Agriculture in cooperation with corresponding research institutes and are submitted to the Ministry of Public Health, en trusted with control duties, for approval. II. General outline of pesticide studies Studying of every new pesticide usually begins with general tox icity determinations (LD50) for some species of experimental animals, followed by its comprehensive studies in plot and field tests and the determination of the pesticidal qualities of a preparation. Simul taneously (if the pesticidal properties are positive) fundamental tox icological studies are carried out to work out specific measures for prevention of hazard and hygienic normalization. Both a pure toxicant and the recommended formulation for its application in agriculture with the whole group of by-products present in a technical grade product and in combination with adjuvants are studied for their toxicity. When studying a new pesticide that belongs to the known class of chemical compounds, having a definite toxicological characteristic, its properties are thouroughly compared with the already known com pounds. Experimental results of the acute and subacute toxicities carried out when investigating a new pesticide make it possible to get an idea of the place a new pesticide occupies among the known substances of this class and to plan its further studies. Comparison of the data obtained for a new compound with the data known for other substances of this class makes it possible, as a rule, to get an idea of the toxicity level. Along with studies of the acute toxicities of pesticides that get into organisms in different ways, great attention is paid to the prob lems of chronic toxicity and to the determination of the cumulative properties of a pesticide. To determine chronic toxicity different tests are run, including the method of conditioned reflexes as it is rather 1 sensitive for a given case. 1 Editor's note: See MEDVED', L. I., E. I. SPYNU, and Iu. S. KAGAN: The method of conditioned reflexes in tOxicology and its application for determining the toxiCity of small quantities of pesticides. Residue Reviews 6, 42 (1964). Tolerances in the USSR 3 As is generally known, the cumulative properties of a substance are much dependent on its physical and chemical properties, including persistence in the environment, the rate of chemical transformations in animals, and the rate of their excretion from organisms. In this connection much attention is payed to the studies of pesti cide metabolism in different living organisms and to the determination of metabolite toxicity. A very important section in the outline of new preparation evaluations is the studies of its reaction with different enzymatic systems of animals, which is very important to determine cumulative properties and to learn its mode of action as well. If the cumulation factor is equal to I, or its value is higher, there is no reason to suppose that the given substance is transformed into a more toxic persistent compound in animals, whereas it is possible to expect the formation of more toxic compounds in animals when the cumulation factor is less than I. The toxicity factor allows for toxicity level of a substance to be found since it characterizes the ratio of LD50, which causes death or serious disease of animals given daily repeated doses, to a dose given once and causing the same effect on animals. It should be noted that the level of cumulation is characterized not only by the cumulation factor value hut also in certain cases by the critical dose value, i.e., by the maximum quan tity of substance given to animals daily which will not cause the danger of getting the cumulation effect. In case the pesticide is of low persistence and the foodstuffs do not contain it when harvest takes place, the hygienic studies of this product become easier. With a rare exception all the plant-protecting chemicals are studied in acute, subacute, and chronic tests to find out their ability to cumulation. Acute and subacute tests supply information on toxic doses of a pesticide, symptom complexes of poisoning, and reveal the most easily affected systems in organisms. The latter information makes it possible to define properties, characterizing the abnormal functioning of organisms to use them for chronic long-term tests when studying sensitive animals given small quantities of the substance to find out the minimum effective concentration. The minimum effec tive concentration is a very important criterion to characterize the minimum substance quantity per unit of animal weight, even if it may cause some small deviations from one of the sensitive tests, when the preparation is given daily to animals over ten to 12 months or more. The minimum effective concentration is a starting point for hygienic normalization of pesticide residues in foodstuffs. Particular care has been taken in chronic test performance when studying persistent pesticides capable of remaining in environment and in living organisms. Not only animals kept in conditions of normal reactive abilities but also animals stressed with higher physiological requirements (pregnant, lactating, growing, etc.) are subjected to these tests. 4 N. N. MELNIKOV and M. G. SHEVCHENKO As the influence of chemical substances on animals is rather differ ent the studies of pesticide effect upon biochemical processes, metab olism processes, change of immuno-biological reactance of organism, cell growth, formation of tumors and mutations, depression of em bryonic development, and some other processes, important to deter mine intoxication, are carried out. Particular importance is attached to studies of blastomogenic properties of pesticides, particularly those which can get into foodstuffs even in minimum quantities and hence systematically get into man's organism. As there are not yet exact criteria to determine the harmfulness of chemical compounds depending on the change of these or those biochemical processes going on under their influence, the problem of the possibility of application of every particular substance is decided individually according to the whole complex of its effects on animals with allowance made for persistence and the possibility to accumulate. Determination of shifts of separate links of metabolism is one of the most important factors when studying toxicity of small pesticide con centrations in particular, the change of protein composition of blood serum, and inclusion intensity of radioactive amino acids into plasma and liver proteins. Under the influence of small concentrations of chemical compounds, when using radioactive compounds, rather dis tinct depressions of tissue protein resynthesis are detected much earlier the expressed destruction factors appear. Determination of sulfhydryl groups in blood, liver, and tissue proteins is also worthy of notice. Much consideration is being also given to studies of neuro humoral and vegetative shifts, shifts in the system of adrenal hypo physis-cortex, disfunction of thyroid gland, etc. Biological studies of foodstuffs, treated with pesticides, are carried out along with the study of problems mentioned above. The biological study of foodstuffs is not obligatory, however, if there are methods accurate enough to determine pesticide residues. TIl. Tolerance levels of pesticides in foodstuffs By a tolerance level of pesticide residues in foodstuffs are meant quantities, detected by the modem methods and means of analysis, which cannot cause any pathological changes or diseases when man's organism is daily exposed throughout his lifetime. Certainly, as knowl edge of a given pesticide accumulates and investigation and analysis methods improve, the tolerance level of a particular pesticide in food stuffs may change either higher or lower. The tolerance levels of pesticide residues in foodstuffs are estab lished proceeding from the minimum effective concentration determin ation found in a long-term chronic test on sensitive animals, with regard to cumulative properties of a formulation, its persistence in the environment and in animals, its thermal stability (when cooked),