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

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

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

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

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

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

Epidemiologic study of renal function in copper smelter workers.

A medical cross-sectional examination of a copper smelter work force was undertaken after environmental contamination with lead, cadmium and arsenic had been documented. A total of 920 subjects was examined, including active smelter employees, retired workers and copper mine employees who had never worked in the smelter. Slight to moderate absorption of lead and cadmium was definitely present in the active copper smelter employees, who had significantly higher levels of Pb-B, ZPP and Cd-B than retired employees and miners. Cd-U levels were higher in retired workers, who were also older and had, as a group, longer duration of exposure in the smelter. Cd-U did not exceed 10 micrograms/g creatinine, the level considered critical for nephrotoxicity, in any of the subjects. Median Cd-B level for active workers was 2.75 micrograms/L. Lead absorption was characterized by a relatively small proportion (16.7%) of active employees with Pb-B levels 40 micrograms/dL or higher. We were particularly interested in exploring the possibility that simultaneous exposure to lead and cadmium, although at levels not associated with nephrotoxicity for each metal separately, could result in renal function impairment. Distribution patterns of BUN and serum creatinine levels were unremarkable. Urinary beta 2-microglobulin levels were less than 200 micrograms/g creatinine in 95% of copper smelter employees. There were no significant correlations between urinary beta 2-microglobulin levels and Cd-U, Cd-B, Pb-B and ZPP or between urinary beta 2-microglobulin excretion and serum creatinine or BUN levels. Urinary beta 2-microglobulin levels were significantly correlated with age in the copper smelter workers, but not in the miners. Nevertheless, in the absence of any significant correlations between urinary beta 2-microglobulin and Cd-U, Cd-B, a causal relationship with cadmium absorption cannot be affirmed. That kidney function could be impaired by long-term exposure in the smelter was only indirectly suggested. Effects on renal function at the low levels of cadmium and lead absorption that were observed in this smelter population are minimal

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