Marvin S. Legator

  • Mutagenicity of Pesticides

    Concepts and Evaluation

    Samuel S. Epstein and Marvin S. Legator

    “There are now about 400 substances that, in various forms and combinations, are used as pesticides. It is feasible to test all of these in the near future for mutagenicity in systems that are simple and precise, yet relevant to man.”

    Mutation is defined in this book as any inherited alteration in genetic material which in future generations may lead to a wide range of irreversible abnormalities. There is a growing concern not only that chemical mutagens may pose a potential public health hazard, but that some chemicals may constitute as great a risk as radiation—possibly a more serious one. This is the first book to present recently developed mammalian methodologies for evaluating mutagenic hazards of chemicals such as pesticides. The authors explain that in most cases it is not the initial compound but the metabolic products of a pesticide which will cause trouble. The critical needs for metabolic data in toxicologic testing in general and in mutagenicity testing in particular are emphasized by Dr. Joshua Lederberg in a foreword.

    “... we can calculate that at least 25 percent of our health burden is of genetic origin. This figure is a very conservative estimate in view of the genetic component of such griefs as schizophranie, diabetes, atherosclerosis, mental retardation, early senility, and many congenital malformations. In fact, the genetic factor in disease is bound to increase to an even larger proportion, for as we deal with infectious disease and other environmental insults, the genetic legacy of the species will compete only with traumatic accidents as the major factor in health.... Given how many new, suspicious compounds now pervade the environment, we face a formidable task in putting our genetic house in order.”

    This study is based on the Report of the Advisory Panel on Mutagenicity of Pesticides to the Secretary's Commission on Pesticeds and Their Relationship to Environmental Health. The Panel was composed of internationally recognized authorities in chemical mutagenesis, mutagenicity testing, and toxicology. It has been greatly modified since the original HEW report (1969) and includes tabulations and a cross index of 370 pesticides listed by their common names and synonyms, chemical name and formula (illustrated), major uses, and manufacturers. There is also a literature review on mutagenicity of pesticides which includes the name of the pesticide, the organism in which it was tested, assay system, range, effective minimum dose, and biological effect. For example, CAPTAN (orthocide) is used as a protectant eradicant fungicide for fruits, vegetables, and flowers in control of scabs, blotches, rots, and mildews. It is manufactured by Stauffer and by Chevron. When tested in human embryo cells (L-132 cells, range 10 mcg/ml) it effected the inhibition of DNA synthesis.

    In addition, the book covers structure-activity relations and usage patterns of pesticides, recommends a program for mutagenesis testing, and contains a summary of literature on mutagenicity of pesticides as well as a bibliography on mutagenic and related effects of pesticides and related compounds.

    • Hardcover $17.50


  • Drugs of Abuse

    Drugs of Abuse

    Their Genetic and Other Chronic Nonpsychiatric Hazards

    Samuel S. Epstein

    Discusses the possible hazards of cancer, birth defects, and genetic changes that might result from indiscriminate use of so-called street drugs, therapeutic drugs of common consumption, or by the interaction of any number of drugs with each other or with environmental pollutants such as pesticides and food additives.

    Drugs used for nonmedical purposes – whether obtained on the street or in the local pharmacy – today constitute a major social problem and controversial issue. In a frequency cited statement, the Federal Drug Administration has estimated that in 1962 nine billion doses of amphetamines and 854,000 pounds of barbiturates were produced in the United States with about half of these doses finding illicit channels of distribution. A national prescription audit for 1965 indicated that 167 million prescriptions written for stimulants, sedatives, and tranquilizers were exchanged across the counter for approximately $590 million. Gallup polls taken two years apart (1967, 1969) reveal a remarkable upward trend (an increase of 300-400 percent) in student using marijuana and LSD. It is impossible, however, to design reasonable policies for the social control of these drugs until a great deal more is known about their possible side effects.

    This book reviews existing toxicological information on drugs of abuse, defines the many areas of ignorance about their nonpsychiatric hazards, and indicates productive strategies for future research. The book grew out of a recent conference cosponsored by the Center for studies of Narcotic and Drug Abuse of the National Institute of Mental Health and by the recently formed Environmental Mutagen Society. It discusses the possible hazards of cancer, birth defects, and genetic changes that might result from indiscriminate use of so-called street drugs, therapeutic drugs of common consumption, or by the interaction of any number of drugs with each other or with environmental pollutants such as pesticides and food additives.

    The book first covers the chemistry and sources of drugs of abuse of immediate social impact – marijuana, LSD, the amphetamines, barbiturates (in measure of gross abuse perhaps “the most serious single problem”), heroin, Sernyl, and STP; potential problem drugs – mescaline, Datura, and DMT; and rare drugs such as Psilocybin, Ibogaine, Harmala, and other botanicals and synthetics. Subsequent chapters discuss the epidemiology and nonbehaviorial pharmacology of drugs of abuse and problems created by the practice of polypharamacy for the physician and patient as well as for the drug abuser. Examples are given of a number of drug interactions.

    Next, the authors consider the chronic biological hazards of drugs of abuse – carcinogenic, teratogenic, and genetic – and list certain chemical groups, some of which are present in these drugs, which are known to induce mutations. A final part of the book is devoted to methods for mutagenicity testing and provides an overview of bacterial (Drosophila), plant, and more definitive mammalian genetic approaches that should be used to identify the mutagenic properties of a drug before it is released for public use. Cytogenetic studies, especially those dealing with LSD, are extensively reviewed, and newly established approaches such as the host-mediated and dominant lethal assays are presented. A survey of over 100 references of chromosomal damage induced by drugs of abuse (with studies of LSD predominating) reveals that evidence on the side effects of LSD and other nonpsychiatric drugs is totally inadequate. Psychiatric aspects of drug dependence and abuse and the role of the National Institute of Mental Health in drug abuse problems are discussed in appendixes.

    A note added in press refers to a major recent development: demonstration, in the laboratories of Dr. Marvin Legator of the Food and Drug Administration, Washington, D.C., that the commonly prescribed phenothiazine tranquilizers, trifluoropromazine and chlorpromazine, are mutagenic in mammals in both the host mediated and dominant lethal assays, and that they thus represent potential genetic hazards to man.

    • Hardcover $30.00
    • Paperback $35.00