Environmental asbestos pollution related to use of quarried serpentine rock.

Crushed serpentinite quarried in Montgomery County, Maryland, has been extensively used for paving roads and other surfaces. The mineral assemblage includes antigorite or lizardite as well as chrysotile and tremolite. Air samples taken in the vicinity of serpentine-paved roads show that chrysotile concentrations are about 10(3) times greater than those typically found in urban ambient air in the United States.

Asbestos contamination of parenteral drugs.

Chrysotile asbestos has been found in approximately one third of the samples from two sets of 17 widely used parenteral drugs.

Exposure to asbestos in the use of consumer spackling, patching, and taping compounds.

Analysis of representative samples of spackling, patching, and jointing compounds, purchased at retail stores in the New York City area, has shown that some contain asbestos minerals as well as other biologically active substances. Measurements suggest that home repair work involving the use of such materials may result in exposure to dust at concentrations sufficient to produce disease.

Inorganic particles in cigars and cigar smoke.

A number of crystalline and optically isotopic inorganic materials are used in the manufacture of reconstituted tobacco sheets. These sheets, used primarily in inexpensive cigars, often contain diatomaceous earth, which exists in part in the silica mineral form cristobalite, a known fibrogen. Diatom fragments with this crystalline form have been observed in the main smoke stream of cigars made with these tobacco sheets.

Endemic pleural disease associated with exposure to mixed fibrous dust in Turkey.

Pleural mesothelioma, lung cancer, pleural calcification and fibrosis, and interstitial parenchymal fibrosis have been observed among inhabitants of several villages in south-central Turkey. Earlier reports have stated that environmental and lung tissue samples from this area contained the fibrous zeolite mineral erionite, and this mineral has generally been assumed to be the agent responsible for these endemic pathological conditions in the absence of asbestos outcroppings and usage. Several different kinds of asbestos minerals in addition to erionite have now been found in environmental samples taken from the villages where these diseases occur. The lung tissues of mesothelioma patients from these villages contain both fibrous zeolites and asbestos minerals.

Asbestos as a cofactor in carcinogenesis among nickel-processing workers.

It has been widely assumed, especially in the absence of other explanations, that lung cancer and nasal sinus cancers observed among nickel smelter workers are the result of the carcinogenicity of nickel. Although there may be such influence, supplementary hypotheses are also possible. The nickeliferous ores from at least one major smelter in New Caledonia (excess numbers of cancers have been found in these smelter workers) are derived from serpentinized host rocks which contain large amounts of chrysotile asbestos. Analysis indicates that nickel ores from this area are heavily contaminated by these fibers. The deposits are mined for their nickel content, but workers may be exposed to the asbestos fibers contained in the deposits. Hygiene measures limited to the avoidance of nickel may be inadequate under such circumstances and should be reevaluated so as to prevent the inhalation of asbestos-containing dusts.

Central nervous system dysfunction due to lead exposure.

Central nervous system dysfunction was investigated in workers at a secondary lead smelter by means of performance tests. Correlations between test scores and zinc protoporphyrin levels, a biological indicator of lead toxicity, are statistically significant. This correlation should prove to be useful in current efforts to evaluate effects of lead exposure.

Lymphocyte function of Michigan dairy farmers exposed to polybrominated biphenyls.

Michigan dairy farm residents ate farm products containing polybrominated biphenyls (PBB's) after the accidential contamination of animal feed with the chemical in that state in 1973. The circulating blood lymphocytes of these residents show significant changes. Abnormalities include decreases in the numbers and percentages of peripheral blood lymphocytes that form rosettes with either sheep erythrocytes alone or with sheep erythrocytes sensitized with antibody and complement, increases in lymphocytes with no detectable surface markers ("null" cells), and altered responses to tests designed to evaluate functional integrity of the cells. There appears to be no consistent correlation between the concentration of PBB's in the plasma and the altered lymphocytes. Studies showed that in Wisconsin dairy farm residents and healthy individuals in the New York area who were not exposed to PBB's there were no such abnormalities.

Urinary excretion of modified nucleosides in patients with malignant mesothelioma.

Transfer RNA is the most complex biomacromolecule in both structure and function. The complexity of its structure is caused by a large variety of enzymes which add modifying groups to the four bases after the primary synthesis. The most abundant of these enzymes are the transfer RNA methylases, which add methyl groups at various positions in the macromolecule. These methylating enzymes were found to be, without exception, aberrantly hyperactive in every malignant tumor examined. In turn, every malignant tumor contains a few transfer RNAs that are different in structure from the transfer RNAs in the normal tissue. Again, there is no exception. These are the first qualitatively different biochemical components of every malignant cell, not more or less but different transfer RNAs. The late Alexander Gutman observed that cancer patients excrete in their urine elevated levels of certain methylated bases. From the structure of these bases and our knowledge of their method of synthesis, it became apparent that most of them come from the breakdown of transfer RNA. Their elevation in the urine stems from an extraordinarily high rate of turnover of transfer RNAs in tumor tissue. Highly sophisticated, sensitive methods of analysis were developed for the determination of the modified nucleosides in the urine of cancer patients. When related to the creatinine level of the urine, some of the modified nucleosides and products derived from them were elevated in a large variety of tumors. Perhaps more importantly, it was found that these elevated levels return to normal after effective chemotherapy. Thus, these markers may also be useful in monitoring the effectiveness of therapy. We report here initial studies on the detection of cancer in asbestos workers and possible premalignant conditions in workers with asbestosis.

Transplantation of human malignant mesothelioma into nude mice.

Human pleural malignant mesothelioma was successfully transplanted into nude mice from 2 of 3 patients. The tumor implants of the first generation grew in 6 of 20 mice (30%), with a take of implants of 17 of 32 (53%). Overall, tumors grew from 52 of 80 mice (65%) in a total of 169 of 266 implants (64%) during the first four generations. The mean delay between transplantation and tumor growth was 46 days (range, 18 to 104 days). Pathological examination by light and electron microscopy confirmed the nature of the growing tumors in nude mice. Pathology of transplanted tumors was grossly similar to the human tumors in both first- and second-generation transplants. Up to eight generations have been presently carried out with presence of a human karyotype in transplanted tumors. The potential usefulness of this model with particular reference to chemosensitivity of these tumors will be investigated.

Ventilatory failure due to asbestos pleurisy.

Seven patients are described who had a distinctive syndrome of chest wall restriction caused by asbestos-induced pleural fibrosis. All had severe dyspnea and predominant pleural disease on radiographic examination, with pulmonary function findings of reduced vital capacity, total lung capacity (measured in five patients), and maximal voluntary ventilation. Five patients had ventilatory failure with carbon dioxide retention; four of these have died and one is close to death. Examination of the thoracic organs in five patients showed minimal or no parenchymal fibrosis in three and less severe involvement of the parenchyma than of the pleura in the remaining two. Neoplasms were suspected in three patients because of extension of the pleural fibrosis into the lung. Two of these patients had pleural uptake of 67-gallium citrate attributable to the inflammatory reaction. With the increasing duration since onset of exposure in the nine million workers who have been exposed to asbestos, as well as in other exposed persons, it is expected that additional cases of ventilatory failure caused by asbestos-induced pleural fibrosis will be encountered.

Historical developments and perspectives in inorganic fiber toxicity in man.

The first patient known to have died from asbestosis (1900) began work in 1885, approximately 5 years after the industrial use of asbestos began in Britain. Mineral particles were found in his lungs. No special comment was made of their fibrous nature then nor when the first case was reported in 1924. The various neoplasms attributed to asbestos in the next decades posed an additional question: What influence did the fibrous shape of the particles have on carcinogenic potential? The cogency of the problem was amplified by the identification in humans of asbestos-like neoplasms with a fiber other than asbestos (erionite) and by the production of such neoplasms in experimental animals with a variety of man-made inorganic fibers, often used as substitutes for asbestos. The lessons learned about asbestos may help guide us in evaluating current fiber problems.

Epidemiology of gastrointestinal cancer.

Some 99,000 new cases of cancer of the colon are expected next year, an incidence rate higher than that for both cancer of the lung and cancer of the breast. Evidence from geographic pathology suggests that some environmental factors play a strong role in its etiology. Data obtained in the 1959 survey of one million people by the American Cancer Society and followed since, has failed to show correlation with any of the large number of factors listed. It is suggested that the etiology is one of multiple factors. The synergistic effect of exposure to asbestos and cigarette smoking in the production of bronchogenic carcinoma is demonstrated by data on cohorts of insulation workers. There was also a modest increase in the number of deaths from gastrointestinal cancer in asbestos workers, but smoking did not seem to act in synergistic fashion at that site, except perhaps in the esophagus. Deaths from cancer occurred almost entirely after a period of 20 years or more from initial exposure. The death rate from cancer tended to increase with duration of exposure, but a distinct rise over the expected was seen in those who had been exposed less than one year to amosite dust.

Priorities in the investigation of human health hazards in the plastics and synthetic rubber industries.

Experiences in the past decade provide guidance in selecting priorities for investigation of health hazards in chemical industries. Pride of place should be given to the experience of large industrial populations, in part simply because large numbers of people are at risk and in part because such studies are more likely to give reliable answers. This recommendation has further strength when there is community exposure as well. Parenthetically, large populations provide opportunity to study multiple factor interaction; without this, toxic potential of a single agent may be obscured. Second, investigations should be mounted when there is reason for suspicion, as with particular chemical configurations, observed organ toxicity, animal carcinogenicity, unusual clinical experience ("signal" tumors). It may be added that when agents have already been used several decades, evaluation of human experience with them is now in order, if only to document absence of toxicity. The same recommendations hold for planned introduction of new agents or widened distribution of existing ones, until we have better information concerning validity of "pretesting" programs. Major advances have been made in epidemiological methods for these investigations. These now allow us to successfully focus on small defined groups as well as to manage large populations.

Hemoglobin, serum iron, and zinc protoporphyrin in lead-exposed workers.

In a previous study of secondary lead smelter workers (males), a significant prevalence of low hemoglobin levels (less than 14 g/100 ml) was found; a statistically significant negative correlation between hemoglobin and zinc protoporphyrin was also detected. In the present study serum iron (Fe) levels and total iron binding capacity (TIBC) were included in the investigation of 111 secondary lead smelter workers and 37 nonexposed controls. The distribution and mean values of serum iron and TIBC were found to be in the normal range in the lead exposed workers; there was no significant difference when compared to the control population. There was no significant correlation between blood lead or zinc protoporphyrin and serum iron, TIBC and Fe/TIBC. A statistically significant negative correlation between hemoglobin and blood lead levels was found; the correlation between hemoglobin and zinc protoporphyrin reached a much higher level of significance. The results support the view that anemia (low hemoglobin levels) in lead exposed male workers is related to the heme synthesis inhibiting effects of lead, as reflected by elevated zinc protoporphyrin levels, and is not due to iron deficiency.

Investigation of the health status of Michigan chemical corporation employees.

Clinical findings are reported for a group of 55 employees of the Michigan Chemical Corporation which manufactured FireMaster BP-6 from 1970 to 1974, in addition to a variety of other halogenated fire retardant chemicals. The results are compared with those from a group of male farm residents and consumers from Michigan examined at the same time. An increased prevalence of chest and skin symptoms was observed, compared with farmers. Skin symptoms were more prevalent among former PBB production personnel. Musculosketal symptoms were less prevalent among these workers than among farmers. Serum PBB concentrations are signicantly higher than among farmers. Blood chemistry results were similar for workers and farmers. However, both groups exhibited a significantly higher prevalence of elevated liver function tests (SGOT, SPGT) than a control population of nonexposed farmers. Both farmers and chemical workers showed an association of elevated CEA with serum PBB greater than 10 ppb.

Family clustering of PBB and DDE values among Michigan dairy farmers.

Family clustering of varying levels of serum PBB and DDE was evaluated for 62 Michigan families by using the mean and standard deviation for family units, ranked percentile comparison of family members, and correlation by linear regression of family members. The results indicate that levels of serum PBBs cluster within family units and for children within families. Serum DDE clustering within families occurs only for children. These findings are consistent with recent, interim PBB exposure, perhaps from a common dietary source for families. Serum DDE represents a lifetime, low-level exposure to DDT-DDE which has been both less prolonged and less intense for children. Thus similar levels, or clustered serum DDE, was observed for children within families.

Comparison of findings among residents on Michigan dairy farms and consumers of produce purchased from these farms.

Consumers who had purchased farm products from both quarantined and nonquarantined farms were examined during the cross-sectional clinical survey of 1,029 Michigan residents. Since PBB had inadvertently contaminated cattle and other farm animals, ingestion of meat, milk, eggs and other farm products was thought to have possibly resulted in significant PBB body burdens in some consumers. Findings were considered in comparison with those made among farm residents. Prevalence of symptoms in consumers of farm products from quarantined farms (CQ) was similar to that found in farmers on quarantined farms (FQ); the prevalence was lower in consumers of products from nonquarantined farms (CNQ). Liver function abnormalities were found with similar prevalence in dairy farmers and consumers. Distribution, mean and median values of PBB serum levels in consumers were found to be similar to those of dairy farmers. These results indicate that significant body burdens of PBB had been accumulated by some consumers of farm products in Michigan and that prevalence of symptoms and liver function abnormalities resembled those found among dairy farm residents.

Unanticipated prevalence of symptoms among dairy farmers in Michigan and Wisconsin.

Adverse human health effects resulting from exposure to polychlorinated biphenyls (PBBs) were unknown until the accidental contamination of Michigan dairy farm animal feed in 1973-1974. Human exposure resulted from the consumption of contaminated meat, milk, dairy products, and eggs. In November 1976, the Environmental Sciences Laboratory conducted comprehensive examinations of 933 farmers and residents in Mighigan who were likely to have consumed farm products contaminated with PBB. A comparison group of 229 Wisconsin dairy farmers were examined in March 1977 and the same scientific and medical staffs that conducted the Michigan survey were responsible and the same procedures used. A complete history of symptomatology by organ system, including year of first onset, duration, frequency, and severity of each symptom was obtained by a physician on all adults examined. Statistical analysis of the prevalence of symptoms at the time of examination or during the preceding year in the Michigan and Wisconsin populations studied found the Michigan group to have a significantly higher prevalence of skin, neurological and musculoskeletal symptoms. The increase was seen among the younger age groups 16-35 and 36-55. Michigan females had a higher prevalence of neurological symptoms than the Michigan males. The existing differences could not be explained without considering an etiologic role for exposure to PBB.

Liver function tests among Michigan and Wisconsin dairy farmers.

Serum activity of SGOT, SGPT, LDH, and alkaline phosphatase was measured in 614 Michigan adults exposed to PBB and 141 Wisconsin adults not so exposed. The Michigan group had higher prevalence of abnormal SGOT (p less than 0.005) and SGPT (p less than 0.005). A clear sex difference was observed. Michigan men had a higher prevalence of abnormal SGPT (p less than 0.005) and LDH (p less than 0.005) than Michigan women, and a higher prevalence than Wisconsin men of abnormal SGOT (p less than 0.005) and SGPT (p less than 0.01). These differences could not be ascribed to differing patterns of alcohol consumption, laboratory error, or choice of criteria for normality/abnormality. Seven Michigan subgroups were defined on the basis of the criteria by which they had been selected to participate. The two subgroups who were essentially self-invited did not differ from the remaining five randomly selected subgroups combined in prevalence of these abnormal liver function tests. Based on 364 serum PBB analyses thus far analyzed of the 614 Michigan participants, no obvious relationship between serum PBB values and liver function tests was observed. However, this is a tentative conclusion that will be further evaluated when remaining serum PBB analyses are completed. The greater prevalence of abnormal SGPT and SGOT among Michigan dairy farm residents compared to the Wisconsin dairy farm residents is tentatively ascribed to the former group's exposure to PBB.