Adverse effects of lead on human health have been recognized for centuries. Nevertheless, current public health measures require a greater understanding of the pathobiology of chronic low level exposure (1-3). Such considerations are related to the question of what level of lead intake is harmful and why specific clinical manifestations of lead poisoning are encountered under particular circumstances. The recognition of factors, both synergistic and antagonistic, which influence the toxicity of lead is essential for adequate understanding of the effects of environmental lead on human health. The immense body of literature already written about lead contains many clues to and impressions of such factors, both adverse and beneficial, modifying the toxicity of lead. This brief review will discuss a number of such factors. Few of these have as yet been subjected to rigorous experimental confirmation. A consideration of antagonisms and synergisms is based on certain assumptions with regard to the metabolism of lead; that is, the daily intake and excretion of lead as well as the movement of lead between various tissues and effects on cells and subcellular organelles.

Susceptibility to lead toxicity.

OBJECTIVES:: Occupational medicine lies at the interface between work and health. Not only do workplace hazards impact health, but our state of health influences our ability to get to work, to perform work, to tolerate work, and to gain a measure of satisfaction from the work we do. Comprehensive occupational medicine requires familiarity with the work that patients do; knowledge of the workplace itself and its hazards; appreciation of the social forces that shape work; and understanding of how chemical, physical, biologic, mechanical, and psychosocial agents influence health. Many practitioners who treat injured workers or provide disability assessments have no more formal training in occupational medicine than primary care physicians in general, which limits the quality, or at least the scope, of the care they give to workers. METHODS:: This history has been compiled from books, journals, letters and recollections. A subset of journal issues from each decade after 1910 has been systematically reviewed, making no attempt to read through every issue. RESULTS:: Industrial medicine as we recognize it began in the late-1800s, grew rapidly in the early and mid-1900s, and peaked toward the end of the 20th century, when American corporations began to outsource medical services, supporting the rise of free-standing industrial medicine facilities, chains of which now operate profitably throughout the country. Many of these facilities emphasize injury treatment, work hardening, and physical therapy rather than disease recognition and prevention. Occupational medicine is one of the very few medical specialties to be underserved. Board-certified specialists are relatively few, and when supply falls short of demand, the demand has tended to lower its sights. CONCLUSIONS:: Occupational medicine has always been influenced by economics, politics, and changing patterns of employment, and today these forces include managed care, weakened unions, outsourcing and contract labor, and a generally growing political and social conservatism, not to mention multinational corporations. The globalization of manufacture and economics facilitated by rapid population growth in poor nations assures an unending supply of cheap labor, allowing limited attention to hazard control, thereby impeding progress in occupational health and safety. Some corporations are meeting the challenge of protecting their international workforce. Many, probably most, have not yet achieved this.

Occupational medicine practice in the United States since the industrial revolution.

Alpha1-antitrypsin (α1) is a glycoprotein in human serum that inhibits the enzymatic activity of trypsin and other proteolytic enzymes. Its concentration in normal serum is 200–250 mg/100 ml. In certain physiological and pathological situations, such as pregnancy, under contraceptive medication and during inflammation, the level of α1-at is elevated. The physiological role of α1 is not known, but the interaction with proteolytic enzymes from white blood cells is probably important. Electrophoretic techniques distinguish several phenotypes, which can be explained by the existence of several codominant alleles at one locus (probably the structural locus). Two alleles PiZ and PiS cause low concentrations of α1-at in serum: the approximate concentrations of α1-at for the different phenotypes are Z/Z 10%, M/Z 50–60%, S/S 60%, M/S 80%, where the level of 212 mg/100 ml found in the M/M phenotype is taken as 100%; thus the effect of these alleles on the α1-at concentration is additive. Homozygosity for the PiZ allele is strongly associated with chronic obstructive lung disease and there is also an association of COPD and heterozygosity for the PiZ or PiS or both, but to a lesser degree.

Alpha-1-antitrypsin: physiology, genetics and pathology.

The premises on which the concept of thresholds of toxicologic response rest are presented and discussed In light of recent, seemingly conflicting evidence from nontoxicologic quarters. Review of the metabolic factors governing toxicologic response, particularly homeostasis and adaptation, makes a good case for the existence of thresholds for chemical substances generally. Possible exceptions are certain natural body metabolities and long-wave ionizing radiation. Finally, the procedures that have to be taken to modify thresholds for the development of appropriate industrial air standards are presented.

Concepts of thresholds in standards setting. An analysis of the concept and its application to industrial air limits (TLVs).

Seventy persons who believed they had been injured by inhaling noxious fumes in the workplace and who consequently filed claims for Workers' Compensation benefits were studied. In most cases medical and psychiatric examinations found no organic basis to substantiate the existence of an organic syndrome. The subjects can be divided into two groups. Those in the first group regarded themselves as intact prior to their exposure to toxic fumes at work; while there was clear evidence of exposure to toxins in these cases, there was not evidence to support the subjects' claims of residual injury. Subjects in the second group first experienced symptoms and then became concerned. Subsequently they and some physicians explained the changes as consequences of the inhalation of toxins in the workplace. A small number of these individuals were diagnosed as "chemically hypersensitive." The premorbid personality traits, behaviors, and patterns and functions of disability that were observed are described.

Mountain Jt

Papers

Progress in detecting the worker hypersusceptible to industrial chemicals.