Despite numerous studies, the role of chemical factors in causing cardiovascular diseases is still disputed, but probably is small. The calculation of the aetiological role of chemical occupational factors for cardiovascular diseases for the Danish population resulted in a value under 1% (Kristensen 1994). For a few materials such as carbon disulphide and organic nitrogen compounds, the effect on the cardiovascular system is generally recognized (Kristensen 1994). Lead seems to affect blood pressure and cerebrovascular morbidity. Carbon monoxide (Weir and Fabiano 1982) undoubtedly has acute effects, especially in provoking angina pectoris in pre-existing ischaemia, but probably does not increase the risk of the underlying arteriosclerosis, as was long suspected. Other materials like cadmium, cobalt, arsenic, antimony, beryllium, organic phosphates and solvents are under discussion, but not sufficiently documented as yet. Kristensen (1989, 1994) gives a critical overview. A selection of relevant activities and industrial branches can be found in Table 1.
Table 1. Selection of activities and industrial branches that may be associated with cardiovascular hazards
|
Hazardous material |
Occupational branch affected/use |
|
Carbon disulphide (CS2 ) |
Rayon and synthetic fiber fabrication, rubber, |
|
Organic nitro-compounds |
Explosives and munitions manufacture, |
|
Carbon monoxide (CO) |
Employees in large industrial combustion |
|
Lead |
Smelting of lead ore and secondary raw |
|
Hydrocarbons, halogenated hydrocarbons |
Solvents (paints, lacquer) |
The exposure and effect data of important studies for carbon disulphide (CS2), carbon monoxide (CO) and nitroglycerine are given in the chemical section of the Encyclopaedia. This listing makes clear that problems of inclusion, combined exposures, varying consideration of compounding factors, changing target sizes and assessment strategies play a considerable role in the findings, so that uncertainties remain in the conclusions of these epidemiological studies.
In such situations clear pathogenetic conceptions and knowledge can support the suspected connections and thereby contribute to deriving and substantiating the consequences, including preventive measures. The effects of carbon disulphide are known on lipids and carbohydrate metabolism, on thyroid functioning (triggering hypothyroidism) and on coagulation metabolism (promoting thrombocyte aggregation, inhibiting plasminogen and plasmin activity). Changes in blood pressure such as hypertension are mostly traceable to vascular-based changes in the kidney, a direct causal link to high blood pressure due to carbon disulphide has not yet been excluded for certain, and a direct (reversible) toxic effect is suspected on the myocardium or an interference with the catecholamine metabolism. A successful 15-year intervention study (Nurminen and Hernberg 1985) documents the reversibility of the effect on the heart: a reduction in exposure was followed almost immediately by a decrease in cardiovascular mortality. In addition to the clearly direct cardiotoxic effects, arteriosclerotic changes in the brain, eye, kidney and coronary vasculature that can be considered the basis of encephalopathies, aneurysms in the retina area, nephropathies and chronic ischaemic heart disease have been proven among those who are exposed to CS2. Ethnic and nutritionally related components interfere in the pathomechanism; this was made clear in the comparative studies of Finnish and Japanese viscous rayon workers. In Japan, vascular changes in the area of the retina were found, whereas in Finland the cardiovascular effects dominated. Aneurysmatic changes in the retinal vasculature were observed at carbon disulphide concentrations under 3 ppm (Fajen, Albright and Leffingwell 1981). Reducing the exposure to 10 ppm clearly reduced cardiovascular mortality. This does not definitively clarify whether cardiotoxic effects are definitely excluded at doses under 10 ppm.
The acute toxic effects of organic nitrates involve widening of the vasa, accompanied by dropping blood pressure, increased heart rate, spotty erythema (flush), orthostatic dizziness and headaches. Since the half-life of the organic nitrate is short, the ailments soon subside. Normally, serious health considerations are not to be expected with acute intoxication. The so-called withdrawal syndrome appears when exposure is interrupted for employees with long-term exposure to organic nitrate, with a latency period of 36 to 72 hours. This includes ailments ranging from angina pectoris up to acute myocardial infarction and cases of sudden death. In the investigated deaths, often no coronary sclerotic changes were documented. The cause is therefore suspected to be “rebound vasospasm”. When the vasa-widening effect of the nitrate is removed, an autoregulative increase in resistance occurs in the vasa, including the coronary arteriae, which produces the above-mentioned results. In certain epidemiological studies, suspected associations between exposure duration and intensity of organic nitrate and ischaemic heart disease are considered uncertain, and pathogenetic plausibility for them is lacking.
Concerning lead, metallic lead in dust form, the salts of diva- lent lead and organic lead compounds are toxicologically impor- tant. Lead attacks the contractile mechanism of the vasa muscle cells and causes vascular spasms, which are considered causes for a series of symptoms of lead intoxication. Among these is tem- porary hypertension that appears with lead colic. Lasting high blood pressure from chronic lead intoxication can be explained by vasospasms as well as kidney changes. In epidemiological studies an association has been observed with longer exposure times between lead exposure and increased blood pressure, as well as an increased incidence of cerebrovascular diseases, whereas there was little evidence of increased cardiovascular diseases.
Epidemiological data and pathogenetic investigations to date have produced no clear results on the cardiovascular toxicity of other metals like cadmium, cobalt and arsenic. However, the hypothesis that halogenated hydrocarbon acts as a myocardial irritant is considered certain. The triggering mechanism of occasionally life-threatening arrhythmia from these materials presumably comes from myocardial sensitivity to epinephrine, which works as a natural carrier for the autonomic nervous system. Still being discussed is whether a direct cardiac effect exists such as reduced contractility, suppression of impulse formation centres, impulse transmission, or reflex impairment resulting from irrigation in the upper airway region. The sensitizing potential of hydrocarbons apparently depends on the degree of halogenation and on the type of the halogen contained, whereas chlorine-substituted hydrocarbons are supposed to have a stronger sensitizing effect than fluoride compounds. The maximum myocardial effect for hydrocarbons containing chlorine occurs at around four chlorine atoms per molecule. Short chain non-substituted hydrocarbons have a higher toxicity than ones with longer chains. Little is known about the arrhythmia-triggering dosage of the individual substances, as the reports on humans predominantly are case descriptions with exposure to high concentrations (accidental exposure and “sniffing”). According to Reinhardt et al. (1971), benzene, heptane, chloroform and trichlorethylene are especially sensitizing, whereas carbon tetrachloride and halothane have less arrhythmogenic effect.
The toxic effects of carbon monoxide result from tissue hypoxaemia, which results from the increased formation of CO-Hb (CO has 200-times greater affinity to haemoglobin than does oxygen) and the resulting reduced release of oxygen to the tissues. In addition to the nerves, the heart is one of the organs that react especially critically to such hypoxaemia. The resulting acute heart ailments have been repeatedly examined and described according to exposure time, breathing frequency, age and previous illnesses. Whereas among healthy subjects, cardiovascular effects first appear at CO-Hb concentrations of 35 to 40%, angina pectoris ailments could be experimentally produced in patients with ischaemic heart disease already at CO-Hb concentrations between 2 and 5% during physical exposure (Kleinman et al. 1989; Hinderliter et al. 1989). Deadly infarctions were observed among those with previous afflictions at 20% CO-Hb (Atkins and Baker 1985).
The effects of long-term exposure with low CO concentrations are still subject to controversy. Whereas experimental studies on animals possibly showed an atherogenic effect by way of hypoxia of the vasa walls or by direct CO effect on the vasa wall (increased vascular permeability), the flow characteristics of the blood (strengthened thrombocyte aggregation), or lipid metabolism, the corresponding proof for humans is lacking. The increased cardiovascular mortality among tunnel workers (SMR 1.35, 95% CI 1.09-1.68) can more likely be explained by acute exposure than from chronic CO effects (Stern et al. 1988). The role of CO in the cardiovascular effects of cigarette smoking is also not clear.