All foreign chemicals are capable, at sufficient concentrations, of producing harmful effects on living tissues. From the time of the Industrial Revolution through most of this century, man ignored the spilling of chemicals into the workplace and the environment. Alice Hamilton, the matriarch of industrial medicine and the first woman on the Harvard faculty, was the first American physician to devote a career to industrial medicine. In her autobiography, she commented, “American medical authorities had never taken industrial disease seriously … The employers could, if they wished, shut their eyes to the dangers their workers faced, for nobody held them responsible, while the workers accepted the risks with fatalistic submissiveness as part of the price one must pay for being poor.”<sup>23 Hamilton A. Exploring the Dangerous Trades Boston: Little Brown (1943).  1

Cliccare qui per andare alla sezione Riferimenti</sup> It would take the enlightened and somewhat startling observations of Rachel Carson in her 1962 book Silent Spring<sup>6 Carson R.L.   Silent Spring Cambridge: The Riverside Press (1962). 

Cliccare qui per andare alla sezione Riferimenti</sup> to awaken the general public, industry, and the scientific world. Twenty-six years later, Hyman Zimmerman<sup>90 Zimmerman H.J. Hepatotoxicity: Adverse effects of drugs and other chemicals on the liver New York: Appleton-Crofts (1978).  333

Cliccare qui per andare alla sezione Riferimenti</sup> commented that

The issues have been clouded, however, by the incompleteness of the database, and the judgements are compromised by the efforts to balance the potential and proved adverse effects of many pollutants against the important, sociologic, economic, and medical benefits… . Containment of the risks posed by environmental contamination requires systematic and coordinated epidemiologic, toxicologic and clinical studies to set the stage for the proper control measures.

Although many of the toxicologic studies have been completed and have led to the eventual removal of some industrial toxins, epidemiologic and clinical studies are still lacking. In fact, fewer than 30% of currently available and potential hepatotoxic chemicals have been studied adequately (more on that later). Dr Zimmerman's comments remain applicable almost one decade later. We continue to have toxic exposures to known hepatotoxins, such as vinyl chloride<sup>56 Pirastu R., Combe P., Reggiani A. , e al. Mortality from liver disease among Italian vinyl chloride monomer/polyvinyl chloride manufacturers Am J Ind Med 1990 ;  17 : 155  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> and yet-to-be-identified hepatotoxins spilling into the environment. A recent observation of nonalcoholic steatohepatitis (NASH) in workers in the petrochemical industry in Brazil, and the resolution of NASH when the workers were moved from the industrial area, is yet another reminder that all is not well.<sup>12 Cotrim H.P., Freitas L.A., Parana R. , e al. Non-alcoholic steatohepatitis (NASH) and environmental toxins: A liver disease in workers from an industrial area Hepatology 1986 ;  24 : 337

Cliccare qui per andare alla sezione Riferimenti, 13 Cotrim H.P., Parana R., Portugal M. , e al. Non-alcoholic steatohepatitis (NASH) and industrial toxins. Follow up of patients removed from one industrial area Hepatology 1997 ;  26 : 149

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Science continues to be compromised by the lack of good models to predict toxicity; the employment of mostly acute rather than chronic studies; and the persistence of economic, social, medical, and political forces, whose diverse priorities have made it difficult to achieve balance. It seems self-evident that a person's health is, in a large part, a function of the health of his or her environment. But even in retrospect, as Dr Zimmerman pointed out, it would be difficult to weigh the benefits of the insecticide dichlorodiphenyltrichloroethane (DDT) against its adverse effects. Although it had devastating effects on wildlife and created havoc with various ecosystems, DDT played a major role in improving the health of that environment by eradicating malaria and enhancing food production in the world.

The important developments in the understanding of metabolic activation of chemicals and the consequences of activation on the interaction of multiple pollutants is just beginning to be recognized. The problem is compounded by the fact that experimental animals have not been highly predictive of human toxicity. A good example was trinitrotoluene (TNT), which was reported to be toxic in 1916,<sup>38 Livingston-Learmouth A., Cunningham B.M. Observations on the effects of trinitrotolune on women workers Lancet 1916 ;  2 : 261

Cliccare qui per andare alla sezione Riferimenti</sup> but toxicity could be shown in animals only after extreme manipulation.<sup>24 Himsworth H.P.   The Liver and its Diseases : Harvard University Press (1947). 

Cliccare qui per andare alla sezione Riferimenti</sup> There also is the problem of acute versus chronic exposure, which may not only have different effects but effects on different target organs. For example, acute exposure to polychlorinated bipheynls primarily involves the skin, although chronic exposure affects primarily the liver. Most models of toxicity test for acute exposure because it is difficult and expensive to test for toxicity to chronic exposure. Despite current shortcoming in methodology, it is no longer possible to introduce a chemical without prior biologic testing. Acceptable exposure limits have been defined by the Occupational Health and Safety Administration. Most important, reports of industrial hepatotoxicity are now rare. Nevertheless, the latency period between exposure and the development of significant toxicity, as well as the persistence of injury after discontinuing exposure (e.g., vinyl chloride), are a constant reminder of the need for vigilance.<sup>25 Ho S.P., Phoon W.H., Gan S.L., Chan Y.K. Persistent liver dysfunction among workers at a vinyl chloride monomer polymerization plant J Soc Occup Med 1991 ;  41 : 10

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The compilation of central databases has helped enormously in making information accessible to the medical, lay, and industrial communities. We have relied on some of these databases in compiling this article.<sup>2 American Conference of Governmental Industrial Hygienists. Internet catalog, 1998

Cliccare qui per andare alla sezione Riferimenti4548 Micromedex Product Fax Sheet. Hall AH, Rumack BH (eds): See what's new with Tones Plus. Englewood, CA, Micromedex, Inc.

Cliccare qui per andare alla sezione Riferimenti, 54 NIOSH. Pocket Guide to Chemical Hazards. U.S. Government Printing Office; 1994. US Department of Health and Human Services Publication 94–116

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This article reviews the mechanisms of injury and exposure, the occupations at risk, the categories of chemicals, and some specific examples of industrial hepatotoxins. It also includes references to information and regulations about industrial toxins.