Evaluates the findings of close to 600 studies aimed at determining whether the health risks associated with tobacco use are enhanced by co-exposure to numerous chemical, biological, and physical agents commonly found in the workplace. Co-exposures in the domestic and general environment, which are especially important in newly industrializing countries, are also considered in this comprehensive review. Although all forms of tobacco use are covered, particular attention is given to risks arising from exposure to mainstream and sidestream smoke from cigarettes. The book has four chapters. The first summarizes what is known about the health risks caused by tobacco use. A brief overview of the history of tobacco use is followed by a detailed explanation of the chemistry of processed tobacco and the many toxic compounds found in tobacco and in mainstream and sidestream smoke. The chapter also includes an overview of all documented acute and chronic adverse effects of tobacco, including smokeless tobacco. The second and most extensive chapter evaluates the evidence on health effects caused by interactions between tobacco smoke and asbestos, non-asbestos fibres, seven inorganic chemicals, five organic chemical agents, including ethanol, four physical agents, and seven biological agents, including two widespread infectious agents. The chapter also includes an explanation of the concept of interaction and how it can be measured, a discussion of vector effects, whereby cigarettes become contaminated with toxic chemicals in the workplace, and a review of data indicating that tobacco smoking can alter the metabolism of therapeutic drugs and other chemicals. Chapter three considers whether adverseeffects following co-exposure to tobacco smoke and other agents are separate effects or possible interactions. The report found evidence for synergism in the production of adverse effects, including cancer, between tobacco smoking and exposure to asbestos, ethanol, silica, and radiation. The report also found evidence that tobacco smoking affects the health risks of exposure in coal mining, pesticide handling, and in the rubber and petroleum industries. In addition, tobacco smoking can increase the risk of byssinosis produced by exposure to cotton dust, and nasal cancer caused by exposure to wood dusts. On the basis of this evaluation, the final chapter concludes that all possible measures should be taken to eliminate tobacco use, particularly smoking. To avoid interaction with occupational exposure and to eliminate hazards arising from exposure to environmental tobacco smoke, the report concludes that smoking in the workplace should be prohibited.

Progress in Clinical and Biological Research, Volume 397
ENDOTOXIN AND SEPSIS
Molecular Mechanisms of Pathogenesis, Host Resistance, and Therapy
Proceedings of the Fourth Conference of the International Endotoxin Society Held in Nagoya, Japan, October 23-27, 1996
Jack Levin, Matthew Pollack, Takashi Yokochi, and Masayasu Nakano, Editors
Recent breakthroughs in our understanding of the molecular biology of the human immune response have lead to important advances in the recognition and treatment of sepsis. Endotoxin and Sepsis: Molecular Mechanisms of Pathogenesis, Host Resistance, and Therapy compiles the latest basic and clinical research on many aspects of sepsis, including sepsis/SIRS. It provides researchers and clinicians with an up-to-date overview of the critical data and concepts in this rapidly progressing field of inquiry.
Featuring contributions by researchers and clinicians from around the world, this book presents papers covering a broad spectrum of specialized topics in the bacteriology, biochemistry, molecular and cellular interactions, pathophysiology, and pharmacodynamics of sepsis/SIRS. It also presents information on in vivo detection and potential new therapies that target sepsis and its cellular effects. Specific topics covered in Endotoxin and Sepsis: Molecular Mechanisms of Pathogenesis, Host Resistance, and Therapy include:
* Enzymes essential to the biosynthesis of Lipid A and their importance in the design of a new generation of antibiotics
* Recent breakthroughs in the understanding of the role of CD-14 in cellular resistance to infection and its therapeutic implications
* The role of Interleukin 6 in endotoxin-induced inflammatory response
* The molecular mechanisms responsible for endotoxin tolerance
* Unique chemical and biological features of LPS, and natural and synthetic LPS control mechanisms.

Endotoxin and Sepsis: Molecular Mechanisms of Pathogenesis, Host Resistance, and Therapy is must reading for laboratory and clinical microbiologists, immunologists, and other investigators studying bacterial endotoxins, and specialists in internal medicine. It will also be of interest to biotechnology and pharmaceutical researchers involved with the development of new drugs to combat sepsis.

This book evaluates the risks to human health and the environment posed by exposure to copper, a malleable metal found naturally in a wide variety of mineral salts and organic compounds, and in the metallic form. Copper is an essential element for all biota. It is widely used in cooking utensils and water distribution systems, in fertilizers, bactericides, fungicides, algicides, and antifouling paints, and in animal feed additives and growth promoters. Industrial applications include use as an activator in froth flotation and sulfide ores, in the production of wood preservatives, in electroplating, and in the manufacturing of azo-dyes.

Provides authoritative guidelines for the establishment or improvement of national programmes for poison control. Addressed to policy-makers and the administrators of specialized facilities, the book responds to the need for comprehensive advice on the most rationale and effective ways to manage the greatly increased number of poisoned patients seen throughout the world. Strategies for the prevention of poisoning are also described. The guidelines draw on the practical experiences of numerous well-established poison centres in different parts of the world. Although recommended lines of action have universal relevance, the book gives particular attention to the situation in developing countries, where a basic infrastructure for the care of poisoned patients is often absent and special problems arise from the lack of adequate communications, transportation, drugs, and support services. Throughout, emphasis is placed on the role and functions of a poison information centre as a crucial component of any national programme for poison control. The book has nine chapters presented in two parts. Part one provides an overview of the policy issues surrounding decisions to introduce measures, including specialized facilities, for the prevention and management of poisoning. Arguing that a poison information centre should be available in every country, part one also describes the benefits of such centres, outlines their principal functions, and suggests various options for their logical and cost-effective operation. Against this background, part two provides detailed technical advice on how to organize and operate the various facilities and services that make up a comprehensive system for poisoncontrol. Separate chapters describe the functions and requirements of information services, clinical services, and analytical toxicological and other laboratory services, and discuss the importance of toxicovigilance as a strategy for prevention. Subsequent chapters explain how to deal with major emergencies involving toxic chemicals, and outline solutions to the problem, encountered in most developing countries, of obtaining essential antidotes. Part two concludes with advice on the design and content of forms for collecting, storing, and reporting data, followed by a detailed list of the main literature required in a poisons information centre. Additional practical information is provided in a series of annexes, which describe a computer software system for the management of poisons data, reproduce several model record and reporting forms, and classify a large number of antidotes and related agents according to their proven effectiveness and urgency of availability. ..." For those involved in improving safety, this book is a bible... It is very difficult to be critical of this outstanding work ... an essential reference for all those involved in the use and handling of chemicals. For regulators and those concerned with government policy issues, it should be compulsory reading..." - Chemistry and Industry

A practical guide to the laboratory analysis of over 100 substances frequently involved in episodes of acute poisoning. Noting that many hospitals, especially in developing countries, lack the support of analytical toxicology services, the book aims to help laboratory staff perform a range of simple tests known to produce rapid and reliable results for the management of poisoning emergencies. All tests described can be performed without the need for sophisticated equipment, expensive reagents, or a continuous supply of electricity. The manual opens with general information about the organization and functions of an analytical toxicology laboratory, the principles of safe laboratory practice, and the essentials of emergency medicine and intensive care that will influence the laboratory's work. Two chapters, which constitute the core of the manual, describe the many simple analytical tests that can be used to detect and identify poisons, whether in biological fluids or in powders, tablets, or other items found near the patient. The first chapter, on qualitative tests for poisons, sets out a three-part series of tests designed for use as a routine, rapid screen, especially appropriate in the many cases where the identity of the poison is unknown. The second and most extensive chapter provides step-by-step instructions for the performance of qualitative tests and some quantitative methods for 113 specific poisons or groups of poisons. Substances covered range from pesticides and other industrial chemicals, through compounds contained in household products, to pharmaceuticals, plant toxins, and drugs commonly abused.

The practice of performing and managing regulatory air toxic risk assessments requires an exceptionally broadbase of understanding. The information and hands-on skills needed to evaluate the effects of air toxic emissions on human health derive from a broad range of disciplines: engineering, the physical and biological sciences, probability, statistics, and medicine. Dr. Lawrence Gratt's Air Toxic Risk Assessment and Management provides a comprehensive study of the subject of risk assessment, showing how the various disciplines are integrated to carry out this complex process. No other resource combines the basic science underlying risk assessment with the techniques needed to perform the analyses.

Evaluates risks to human health and the environment posed by the use of beryllium, a brittle metal having major applications in the electronics and micro-electronics industries, in nuclear energy, and in the production of military devices, including satellites, missiles, atomic bombs, and other weapons. Beryllium has also proved its superiority as a structural material for aircraft and spacecraft.

Assesses the risk to human health posed by the use of inorganic mercury in dental amalgam and in soaps and creams used to lighten the skin. Although such skin-lightening products are now banned throughout the European Economic Community, in North America, and in many African states, the report reveals that mercury-containing soap continues to be manufactured in several European countries, is sold as germicidal soap to the Third World, and is illegally re-imported from Africa to European cities having a substantial black population. Dental amalgam and food, most notably seafood, are identified as the main sources of human exposure. Although exposure of the general population is judged to be low, toxic levels may arise from the mishandling of liquid mercury, mercury dispensed from jars, broken thermometers, fluorescent lamps, and accidental ingestion of mercury batteries. The use of skin-lightening soap and creams results in substantial exposure.

Evaluates the risks to human health and the environment posed by the production and use of 2-propanol, a liquid widely used as a low-cost solvent in industry and in the home. Because of its cooling, antipyretic, rubefacient, cleaning, and antiseptic properties, 2-propanol is used to produce a large number of household and personal products, including topically applied pharmaceutical products and cosmetics.

Summary Reports the deliberations of a working group convened to evaluate the carcinogenic risk to humans posed by the therapeutic use of 15 pharmaceutical drugs. The volume features separate monographs on five antineoplastic agents, four antimicrobial agents, two diuretics, ciclosporin (an immunosuppressant), cimetidine (used in the treatment of gastric and duodenal ulcers), paracetamol (a popular analgesic and antipyretic drug), and dantron (a laxative). Drugs were selected for inclusion on the basis of published data suggesting carcinogenic effects in experimental animals or in human patients treated with the drug. The working group identified two of the drugs - ciclosporin and thiotepa - as human carcinogens. Ciclosporin, an immunosuppressant, is widely used in the prevention and treatment of graft-versus-host reactions in bone-marrow transplantation and to prevent the rejection of kidney, heart, and liver transplants. Often given to transplant recipients for several months, ciclosporin has been linked to a remarkably high occurrence of lymphomas, found predominantly in the gastrointestinal tract, as well as to skin cancer and Kaposi's sarcoma. The carcinogenicity of thiotepa, a cytostatic agent used in the treatment of malignant lymphomas and solid tumours, has been clearly demonstrated in both experimental animals and human patients, where treatment with the drug has been linked to the development of leukaemia. Azacitidine, chloramphenicol, and chlorozotocin were judged to be probably carcinogenic to humans, while dantron and trichlormethine were identified as possible human carcinogens. The remaining substances could not be classified on the basis of currently available evidence. The experts also noted that long-term experiments with paracetamol, nitrofurantoin, and nitrofural have shown reductions in tumour incidence at some sites in some animal species.

Evaluates the risks to human health and the environment posed by the mining, processing, and industrial use of barium. The opening sections review both natural and man-made sources of release into the environment, including nuclear fallout following the testing of weapons. A section on environmental behaviour notes the contribution of industrial emissions, especially from the combustion of coal and diesel oil, to the presence of barium in air. Particular concern centres on concentrations found in water, where barium may have a residence time of several hundred years. Water supplies and food are identified as the most important routes of exposure for the general population. Other sections review what is known about the kinetics and metabolism of barium, discuss its capacity to mimic the role of calcium in many physiological processes, and consider effects on organisms in the environment, including effects on the infectivity of several viruses.

Evaluates the risks to human health and the environment posed by exposure to acrolein, a chemical produced in large quantities and used as an intermediate in the synthesis of several chemicals, most notably acrylic acid and its esters and DL-methionine, an essential amino acid used as a feed supplement for poultry and cattle. Acrolein also has direct application as an aquatic biocide used against algae, molluscs, and herbs in recirculating process water systems, irrigation channels, cooling water towers, and water treatment ponds. Acrolein accounts for about 3 to 10% of total automobile exhaust aldehydes, 1 to 13% of total wood-smoke aldehydes, and up to 7% of the aldehydes in cigarette smoke. The report notes that exposure of the general population occurs mainly via air, with mainstream and sidestream tobacco smoke representing the most important source. Other sources of exposure include inhalation of air polluted by vehicle exhausts, direct contact with acrolein-treated water, and consumption of alcoholic beverages and certain food items. Concerning effects on the environment, the report cites studies documenting adverse effects on crops grown on soil irrigated by acrolein-treated water, and a very high toxicity for bacteria, algae, crustacea, and fish, with bacteria being the most sensitive species. Acrolein is noted to threaten aquatic life at or near sites of industrial discharge or spills and in areas where acrolein is used as a biocide.

Evaluates risks to human health and the environment posed by the production and use of tricresyl phosphate. Tricresyl phosphate is used in industry as a plasticizer in vinyl plastic manufacture, as a flame-retardant, as a solvent for nitrocellulose, in cellulosic molding compositions, and in the manufacture of fire-resistant hydraulic fluids and lubricants. Because of the physico-chemical properties of tricresyl phosphate and its rapid biodegradation, the report concludes that use of the compound does not threaten the environment, though there is some evidence that crop plants can be affected by tri-o-cresyl phosphate released from plastic coverings. A section devoted to kinetics and metabolism concentrates on mechanisms of absorption, distribution, metabolism, and elimination that can help explain the well-documented neuropathic actions of tricresyl phosphate and, most notably, its highly toxic isomer, tri-o-cresyl phosphate. The most extensive section assesses findings from toxicity studies, emphasizing the large number of studies documenting neurotoxic effects, often at very low doses. These effects are further characterized through a review of the numerous reported cases of large-scale human poisoning following the ingestion of accidentally or deliberately contaminated medicines and foodstuffs. Readers are given detailed information on the clinical symptoms of poisoning, the characteristics of delayed neuropathy, long-term prognosis, and advice on the first-aid treatment of victims. While the concluding section notes that use of tricresyl phosphate poses very little risk to either the environment or the general population, the report underscores the severity and long-duration of the neuropathology caused by accidental poisoning, noting that some victims never recover.

Evaluates close to 900 studies in an effort to determine the role of various nickel compounds as environmental hazards and causes of human diseases, including cancer. A special effort is made to determine the specific exposure levels for nickel and nickel compounds that pose a threat to the environment, the general public, and workers exposed to nickel-containing dusts and fumes. A section on sources of exposure evaluates both natural and man-made releases into the environment, offering especially detailed information on emissions associated with the nickel industry, the combustion of fossil fuels, and the incineration of sewage sludge and waste. Exposure of the general population is noted to occur via inhaled air, ingestion of food and drinking-water, and dermal contact, particularly with jewellery and coins.

Evaluates the risks to human health and the environment posed by exposure to isobenzan. This cyclodiene insecticide was manufactured in the Netherlands from 1958 to 1965 and used from existing stocks for several years thereafter. Present sources of human and environmental exposure are restricted to the original waste-disposal sites and to polders which were built up using mud dredged from contaminated harbour areas. Although recent research on this insecticide has been limited, the report draws heavily on a number of proprietary toxicological studies made available by the manufacturer.

Evaluates the risks to human health and the environment posed by exposure to alpha- and beta-hexachlorocyclohexanes (HCH). These two isomers are by-products in the manufacturing of lindane, and may be present in this pesticide as impurities. Alpha- and beta-HCH are also present in technical-grade HCH, which is used in agriculture and wood protection. Most environmental releases are linked to the use of technical-grade HCH and to the inappropriate disposal of residues produced when lindane is purified.

Evaluates risks to human health and the environment posed by aldicarb, a carbamate insecticide applied, exclusively in granular form and below the soil surface, to control certain insects, mites, and nematodes. Aldicarb has been approved for use on a wide range of crops; ingestion of contaminated food is the main route of exposure for the general population.

Summary Evaluates the carcinogenic risk to humans posed by industrial exposure to chromium and its compounds, nickel and its compounds, and welding fumes and gases. Occupational exposures, principally by inhalation, are noted to affect about three million workers worldwide. The first and most extensive monograph evaluates the carcinogenicity of chromium and its compounds. The monograph is divided into subsections based on the oxidation state and solubility of the compounds, with separate evaluations made for metallic chromium, chromi-um[III] compounds, chromium [VI] compounds, and for a fourth group of tested agents that were of mixed or unknown oxidation states. The most extensive sections evaluate the design and findings of over 500 investigations of carcinogenicity in animals and experimental systems, studies of metabolic fate in animals and humans, and case reports and epidemiological studies in human populations. On the basis of this evaluation, the monograph concludes that chromium[VI] is carcinogenic to humans. The carcinogenicity of chromium[III] and of metallic chromium could not be determined on the basis of available evidence.The second monograph presents similar information for metallic nickel and nickel alloys, nickel oxides and hydroxides, nickel sulfides, nickel salts, and other nickel compounds. Nickel carbonyl is identified as the most acutely toxic nickel compound, causing severe damage to the respiratory system in experimental animals and in humans. The evaluation concludes that nickel compounds are carcinogenic to humans and that metallic nickel is possibly carcinogenic to humans. The final monograph evaluates the carcinogenic risk posed by exposure to welding gases and fumes. On the basis of evidence from human and animal studies, welding fumes are classified as possibly carcinogenic to humans.

Evaluates risks to human health and the environment posed by the use of tributyltin compounds as molluscicides, as antifoulants on boats, ships, quays, buoys, and equipment in the fishing industry, as wood preservatives, and as slimicides on masonry. These compounds pose a particular threat to the marine environment in view of their documented high toxicity to aquatic organisms, including commercially important shellfish.

Evaluates risks to human health and the environment posed by the widespread production and use of methyl isobutyl ketone as a solvent, with major applications in the production of lacquers and paint solvents, including car and industrial spray paints. Methyl isobutyl ketone also occurs naturally in food, is a permitted flavouring agent, and is used in food contact packaging materials. Sections concerned with the behaviour of methyl isobutyl ketone in the environment note its rapid evaporation into the atmosphere, rapid photo-transformation, ready biodegradation, and low potential for bioaccumulation. A review of data on metabolic pathways and toxicity to organisms concludes that production and use of this chemical pose no threat to wildlife or the environment, except in the case of accidental spills or inappropriate disposal of wastes.

Evaluates risks to human health and the environment posed by the production and use of dimethylformamide, an organic solvent produced in large quantities throughout the world. Dimethylformamide is widely used in the chemical industry as a solvent, an intermediate, and an additive, with the largest quantities used in the production of acrylic fibres and polyurethanes. Dimethylformamide is also used in the production of pharmaceutical products.

Evaluates risks to human health and the environment posed by the production and use of triphenyl phosphate, a compound widely used as a flame retardant in phenolic and phenylene-oxide-based resins for the manufacture of electrical and automobile components. Triphenyl phosphate is also used as a non-flammable plasticizer in cellulose acetate for photographic films, and as a component of hydraulic fluids and lubricant oils.

Evaluates risks to human health and the environment posed by the production, use, and disposal of hexachlorocyclopentadiene (HEX). HEX is a chemical used in the production of several pesticides, including heptachlor, chlordane, aldrin, dieldrin, endrin, mirex, pentac, and endosulfan. The compound is also used as an intermediate in the manufacturing of flame retardants and dyes.

Evaluates the risks to human health and the environment posed by n-hexane, a chemical isolated from natural gas and crude oil and used in food processing to extract vegetable oil from beans, nuts, and seeds. n-Hexane is also used as a solvent, a cleaning agent, in the rubber industry, and in the manufacture of pharmaceuticals.

Evaluates the environmental hazards and risks to human health posed by the production and use of vinylidene chloride. Vinylidene chloride/vinyl chloride copolymers are used for the packaging of foods, as metal coatings in storage tanks, building structures, and tapes, and as moulded filters, valves, and pipe fittings. Food packaging applications include both commercial packaging films and household wraps.