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The purpose of this study was to determine the mortality and cancer incidence of long-term lead smelter workers at a primary smelter.A cohort of 3979 workers employed for at least 1 year during 1928-1979 and a subcohort of 1992 workers employed in lead-exposed departments (lead only workers) was formed. The expected mortality in 1955-1987 and cancer incidence in 1958-1987 were calculated relative to the county rates, specified for cause, gender, 5-year age groups, and calendar year. A cumulative blood-lead index was used for the dose-response analyses.The lung cancer incidence of the total cohort [standardized incidence ratio (SIR) 2.8, 95% confidence interval (95% CI) 2.1-3.8] and the group with the highest exposure (SIR 3.1, 95% CI 2.0-4.6) was high. Similar risk estimates were observed with a latency of 15 years. The workers hired before 1950 had higher lung cancer risk estimates (SIR 3.6, 95% CI 2.6-5.0) than the workers hired later (SIR 1.3, 95% CI 0.6-2.6, no latency period). The risk estimates for lung cancer were further elevated in the subcohort of lead-only workers (SIR 5.1, 95% CI 2.0-10.5 in the highest exposed subgroup; latency period of 15 years). No excesses of other malignancies were noted.The increased relative risks were probably mainly due to interactions between lead and other carcinogenic exposures, including arsenic. Further study is required concerning such possible interactions before a role in the induction of lung cancer can be ascribed to lead.

Lacking or deficient description of sampling and analytical quality often occurs in scientific publications involving human biomonitoring. In the present issue of this journal, Gerhardsson et al (1) presents an evaluation of publications on reference values for lead in blood. The authors found only 10 out of more than 1000 papers published between 1980 and 1994 which fulfilled a strict set of evaluation criteria. The expanding number of scientific publications reporting levels of trace elements in human tissues and biological fluids should provide for improved possibilities to define absorbed individual doses in, for example, occupational exposures. In many situations, however, this is difficult because of the lack of access to information about expected "normal" or reference values from occupationally unexposed persons. This problem increases when occupational exposures decrease, as many have done recently, subsequent to the identification of related risks. One main reason for decreasing concentrations in occupationally exposed persons thus is decreased exposure in the industrial environment. Are reported decreases in "normal" or reference values also explained by decreased exposures? Yes, but only partly. Reported "background" concentrations of such potentially toxic elements as lead, nickel, chromium, and cadmium in occupationally unexposed persons have decreased substantially, sometimes by a factor as large as 1000 (eg, chromium). The reasons for this decrease in reported concentrations are many, and some have not become obvious until a systematic and critical evaluation of published data has been undertaken. Several scientists have identified problems in sampling and analysis, but a systematic approach was not taken until an international group of scientists working under the name TRACY (2) was formed on the initiative of the Scientific Committee on Toxicology of Metals within the International Commission on Occupational Health and the Commission on Toxicology within the International Union of Pure and Applied Chemistry. In addition to the TRACY evaluations of published data, the Commission on Toxicology has recently published "Sample Collection Guidelines for Trace Elements in Blood and Urine" (3). Evaluations by the TRACY Group (1, 2, 4--7) have shown that there are different reasons for the decreases reported for the various elements. It has, for example, become obvious that most of the decrease in the reported concentrations of nickel and chromium in serum are related to improved control of sampling contamination (stainless needles). For nickel in serum, a measurement increasingly used to evaluate absorbed doses in industrial workers, values reported for occupationally unexposed persons have decreased substantially during the last decade (4), and this decrease has probably been mainly due to improved control over contamination during sampling. However, even for values reported more recently, sufficient control over this error has not always been achieved, and this factor still plays a role in influencing reported values (4). The same situation may be true for chromium (5), and, in addition, several other factors can be expected to influence the values of these two elements. Before analytical and contamination factors are under control, it is not possible to identify other factors, such as dietary intake and internal exposures from prosthetic devices, that are likely to influence the values (5). As pointed out by Gerhardsson et al in this issue (l), the decreases for lead are only to a limited degree related to contamination problems in sampling, and most of the decrease is actually related to decreased exposure of the general public. This critical evaluation according to the TRACY protocol has indicated that, for lead in blood, several factors are important, such as age, gender, ethnicity, food, drinking and smoking habits, hobbies, season and year of sampling, residential area, and geographic location. Since lead in blood is dependent on exposure time and is area specific, it is obvious that it is not possible to present a general overall reference value for lead in the blood of nonoccupationally exposed populations. Instead, it is obvious that the values obtained from occupationally exposed persons must be compared with those of reference groups displaying the same general characteristics as the occupationally exposed group, except for the occupational exposure. It has been attempted, within the framework of the TRACY criteria, to define more generally applicable reference values. A description of prerequisites and methods, taking cadmium in blood as an example, has been presented by Alessio et al (6). It was obvious however that also for that element all available data could not be accommodated into one common range but that consideration needs to be taken of smoking habits, since they influence blood cadmium values substantially. In addition, specific consideration was necessary for certain areas of the world where dietary cadmium intake is higher than elsewhere. As pointed out in the evaluation of lead (1), geographic variation may be common, and, for most elements, reference values applicable in large geographic areas may not be possible to define. For cadmium, no important temporal variations could be demonstrated, like those shown for lead. For selenium, however, important annual differences have been shown to exist, depending on fluctuations in dietary intake (7). The evaluation for selenium further demonstrated the usefulness of the TRACY criteria also for an essential element, and it is expected that further evaluations of other essential elements may be forthcoming. A main conclusion from the TRACY project, so far, is that there are too few publications that contain adequate descriptions of sampling and analysis and therefore only a very small proportion of published data is useful for a discussion of true reference values when strict criteria are applied. This small amount of data makes it easy to select the papers that fulfill the criteria and also to select reliable values, but for several elements the possibilities to identify true factors including variations in background exposure are seriously limited because errors in sampling (including contamination) obscure such variation. It seems obvious that there is still a need for continuous critical evaluation of published data on trace elements in human biomonitoring, and the TRACY project can be expected to produce interesting reports in the future. It seems peculiar that, in spite of seemingly adequate peer review in reputable journals, so many papers have been published which lack appropriate documentation of quality control. This lack may be due to the editorial policies of some scientific journals according to which authors are discouraged from presenting full population descriptions, sampling details, and analytical performance data in a single manuscript. Editors would be well advised to change such policies and pay more attention to these quality aspects when evaluating and accepting manuscripts for publication.

This paper discusses metal exposure in the male, the nonpregnant female, and the maternal-offspring unit. In the first two situations, the primary targets are the gonads. In the mother-offspring unit, consideration must be given to effects on the fertilized ovum, the growth of the embryo, and, finally, to the fetal and perinatal stages. The central nervous system may be especially vulnerable during development. The placenta also undergoes development, and either the placenta or the fetus may be the primary target. In humans, certain metals may cause abortion or other effects on the conceptus. Effects may also be produced by metal exposure both in utero and in the suckling infant. For example, methylmercury gives rise to a range of effects on the central nervous system at doses lower than those producing damage to the mature nervous system. Effects of lead and arsenic are associated mainly with postnatal exposures during infancy and early childhood, but there is reason to believe from animal experiments that some effects may occur from prenatal exposures to certain metal compounds.

Airborne factory dust (with a volume median diameter of 5.0 micron and a geometric standard deviation of 2.1 micron) from a Swedish copper smeltery contained antimony (Sb) (1.6 weight %) and arsenic (As) (19 weight %). The dust was neutron activated and intratracheally instilled in hamsters. In vivo measurements of lung clearance were undertaken of the radionuclides 76As, 122Sb, and 124Sb. Comparison was made with pure substances of antimony trioxide (Sb2O3) and arsenic trioxide (As2O3). Two phases were recognized in the clearance curves. The approximate half-time for the initial phase was 13 h for As2O3, 20 h for arsenic dust, about 40 h for Sb2O3, and about 30 h for antimony dust. The second phase had an approximate half-time of 20-40 d for Sb2O3 and antimony dust. Because of the short physical half-life of 76As, the second phase of the lung clearance was not possible to follow for AS2O3 and arsenic dust. The observed differences in clearance were primarily related to the solubility of the dust particles in saline, while particle size seemed to be less important in this instillation experiment. The low solubility of antimony in factory dust combined with a long biological half-time may be of importance in explaining the observed lung accumulation of antimony in exposed workers. The greater solubility and shorter biological half-time restricted the lung retention of arsenic.

Tissue concentrations of antimony in lung, liver, and kidney tissue from a group of deceased smelter workers from northern Sweden have been compared with those of a group of persons without occupational exposure from a nearby area. Neutron activation analysis was used to determine the antimony concentration of lung tissue from exposed workers; these concentrations were 12-fold higher than those of referents (p less than 0.001). For lung tissue there was no tendency towards decreased antimony concentrations with time (up to 20 a) after the cessation of exposure, and this result indicates a long biological half-time. The highest values were found for workers who had worked for many years at the roasters and in the arsenic and selenium departments. There was no significant difference between the antimony concentration of the lung tissue from workers who had died of lung cancer and those of persons who died of other malignancies, cardiovascular disease, or other causes. This finding does not however rule out the possibility of a role for antimony in the etiology of lung cancer among smelter workers since multiple factors may have been operating. The antimony concentration of the liver tissue and the kidney cortex did not differ from the corresponding values of the reference group; this finding indicates either a short biological half-time or insignificance for the systemic distribution of antimony.

A worker was buried under arsenic trioxide in an industrial accident. He was almost immediately released but had inhaled and swallowed substantial amounts of arsenic dust. In spite of intensive treatment, circulatory collapse could not be prevented, and he died 6 h after the exposure. The treatment, autopsy findings, and arsenic concentrations in tissues and body fluids are described and discussed.