TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS
5.3.1 Introduction and Background
5.3.1.1 Health Hazards Due to Occupational Exposure
Workers exposed to chemicals often experience discomfort and adverse
Health effects which may progress to occupational diseases. Even though
Working conditions have improved markedly during recent decades, in general
The number of individuals suffering occupational diseases has declined rather slowly. In addition, the number of new cases of registered occupational health diseases depends on employment circumstances; there is a natural decline during times of economic recession. This gradual change is due to several factors: the diagnostic criteria have become less stringent, physicians have learned to recognize occupational diseases better, and many occupational diseases develop slowly and thus the present situation reflects, at least to some extent, past exposures. Furthermore, the significance of occupational allergies has increased and allergic reactions can be caused even by low exposure levels.
Toxic chemicals, such as benzene and carbon disulfide, which in the past were common causes of occupational diseases, are nowadays generally well controlled. Most of the current occupational diseases are caused by exposures which are not particularly acutely toxic, but cause allergies. Typical exposures causing allergies are animal and flour dusts. If one considers actual chemicals, then isocyanates have become a major problem, principally via their ability to cause sensitization. Historical exposure to asbestos and other mining dusts still leads to numerous new diseases, many of which are very serious, even fatal. Solvents and pesticides are the groups of chemicals probably causing the largest amount of acute poisoning-type occupational diseases. l>2
Traditionally, the greatest risk due to chemicals has been considered to occur via inhalation. Chemicals may also penetrate through the skin. Water-based products are increasingly replacing solvent-based products in many applications, such as painting, printing, and gluing. The water-based products may, however, contain glycol derivatives which penetrate through the skin with ease. Many chemicals also irritate or sensitize the skin. Chromium, nickel, and epoxy resins are examples of common occupational skin allergens.
Ventilation engineers and occupational hygienists must be aware of the risks of chemicals with a high acute toxicity. Chemicals which are odorless (e. g., carbon monoxide), paralyze the sense of smell (e. g., hydrogen sulfide), or cause pulmonary edema as a delayed effect (e. g., nitrogen dioxide and ozone) are especially insidious. Often these gases are produced as unwanted by-products. For example, nitrogen dioxide and ozone may be formed due to oxidation of air during welding. Welding near sources of chlorinated solvents, such as perchlo — roethylene, may cause pyrolysis and the formation of phosgene.
Occupational exposure limits (OELs) have been set in most industrial countries to prevent excessive exposures. The limits for the most common exposures are based on experimental animal and epidemiological studies. Most novel agents have now generally gone through extensive toxicological testing. For the older chemicals, usually a plethora of epidemiological data is available.
When the incidence of occupational diseases was compared with the frequency of OEL violations in Finland, a rather good correlation was observed. This indicates that these OELs are reasonably well defined. This is also natural because they are based on long-term exposure history of a large number of people. However, the OELs for many chemicals are still only educated guesses, and numerous and often large changes have been made when the OEL lists have been revised. In addition, most chemicals still have no OEL. Only about 2000 chemicals have an OEL in some country.3
A particularly strict exposure-control policy is applied for carcinogenic chemicals. The OELs are usually lowered considerably even when a chemical
Is only suspected of being a carcinogen. When the evidence becomes stronger, the OELs are usually tightened further. Vinyl chloride provides a good example; its OEL was first lowered to 20 ppm from 500 ppm and then further to 3 ppm in Sweden in 1974-5 when its ability to cause a very rare type of cancer, angiosarcoma of the liver, was detected. The rarity of the disease made it possible to locate the association; on the other hand, the practical impact of this carcinogenic potency also remains rather low. It has been estimated that less than 400 angiosarcoma cases will appear worldwide due to vinyl chloride exposure (in comparison with the number of occupational cancers caused by asbestos which is already about 1000-fold higher).4-5 Internationally, there is an ongoing vigorous discussion on whether there are possible thresholds for genotoxic carcinogens. In many instances these compounds are considered to have no safe dose. If one assumes that there is some threshold also for genotoxic carcinogens, this would have major consequences for the assessment of risks of carcinogenic compounds.6’8
Since the OELs provide the basis for ventilation requirements, an astute designer tries to find out how secure the OELs of the chemicals which will be used in the plant he or she is planning. Some of the chemicals used may totally lack OELs. Therefore, it is advisable to become familiar with the relevant literature, preferably together with a specialist. It is clear that the ventilation engineer needs to be aware of the possible significance of toxicology for industrial ventilation construction.
The epidemiological data have the advantage of being based on human exposures. However, the results of epidemiological studies often remain inconclusive because of various confounding factors and poor exposure assessments. In addition, epidemiological data are available for only a small number of agents. The target level approach, presented in chapter 6 of this book, uses inherently large safety margins in relation to OELs. Unfortunately, it is also applicable only for the most common exposures. Since zero exposure is the best, the ALARA (As Low As Reasonably Achievable) principle, adopted in radiation protection, is, in principle, also a good approach for other exposures.9’10 However, even then the question, how low is low enough, may remain unanswered. This chapter has been written with the intention of lowering the threshold for a ventilation engineer to seek a toxicological consultation and to provide the fundamental background information needed to utilize the available toxicological literature. Occupational hygienists may also find the text to be a useful compact overview of the essential concepts of toxicology.
Epidemiological studies usually consist of the knowledge obtained from human exposures supplementing data derived from experimental studies. Epidemiological data often provide the ultimate proof of the deleterious effects of a chemical compound on humans, and form an important component of the assessment of the risks of some chemical compounds. In the future, the role of epidemiological data should be confirmatory rather than decisive in the risk assessment of existing and, especially, of new chemicals, since toxicology is becoming more and more a preventive rather than an observational science in protecting the health of workers exposed to chemicals and mixtures of chemi cals in occupational environments.
The purpose of epidemiological studies is to try to identify whether there are causal relationships between the occurrence of diseases or other biological effects and exposures to various agents. There are three main types of epidemiological studies: cross-sectional, cohort, and case-control studies. The working population is, on the average, healthier than the general population. Due to this “healthy worker effect,” comparisons should be made with another worker group instead of the general population. The reason for the healthy worker effect is the fact that it is difficult for sick or disabled people to stay in employment due to the limitation caused by their diseases. Poor health may also prevent a person from getting a job in the first place.
In a cross-sectional study, exposure and effect are studied simultaneously. This approach contains an inherent problem because exposure must precede the effect. However, it can be used to investigate acute effects and also mild chronic effects (which do not force people to leave their jobs) if exposure has remained rather stable for a long time. When the prevalence of the effects studied are compared with the prevalence in other worker groups (controls or references) which correspond otherwise with the study group but are not exposed to the agent investigated, indicative evidence of possible causality may be obtained. For example, cross-sectional studies have been applied successfully to reveal the associations between mild neurotoxic effects and exposure to organic solvents.11
Cohort Studies
In a cohort or follow-up study, a group of workers exposed to the same agent is followed for a certain period, which can be either retrospective (starts at some time in the past and continues to the present) or prospective (starts in the present and continues for a certain time into the future). A cohort of controls should be formed with the same selection criteria as used for the study groups, except that they lack the exposure. Thus, exposure to one agent only can be studied whereas several health outcomes can be included. A cohort study is the only possible study method when the exposure studied is rare. The results of the cohort study are expressed as relative risks (risk ratios, RR) for various diseases (see Table 5.8 for results of different types of epidemiological studies on cancers in printing workers and epidemiological terms) (IARC, 1996),
Relative Risk (RR) = (exPosefd-^……………. diseasej/^U exposed)
(controls with disease)/(all controls)
A,, r> ■ mm (exposed cases)/(non-exposed cases)
Odds Ratio OR) = ———
(exposed controls)/(non-exposed controls)
The benefit of a prospective cohort study is the possibility for accurate exposure assessment. However, these are not common, because many occupational diseases (including cancers which are being intensely investigated currently) require long exposure times to develop. It is not practical or ethical to wait for decades before one obtains the result.
The problems often encountered in retrospective cohort studies include poor exposure data and incomplete follow-up of all individuals. The accuracy of health outcome data may also be low.
Reference, |
Period of |
Cancer site/ |
No. |
||||
Country |
Study subjects follow-up |
Occupation/exposure |
Cause of death |
Obs. |
RR |
95% Cl |
Comment |
Malket and |
24 652 men and 1961-73 |
Printing workers (M) |
Lung |
190 |
1.5 |
[1.3-1.8] |
Morbidity |
Gemne,1 ’ |
6450 women |
Blue-collar workers (M) in |
Lung |
149 |
1.6 |
[1,4-1.9] |
|
Sweden |
Registered at 1960 census as printing workers |
Printing enterprises (newspaper, journal/book printing, others) |
|||||
Birth cohort around 1990 (M) |
Lung |
45 |
1.9 |
1.4-2.5 |
|||
Urinary bladder |
76 |
1.3 |
NG |
P > 0.01 |
|||
Kidney |
48 |
1.1 |
NG |
P > 0.01 |
|||
Skin melanoma |
27 |
1.2 |
NG |
P > 0.01 |
|||
Printing workers (F) |
Lung |
9 |
1.3 |
NG |
P > 0.01 |
||
Urinary bladder |
5 |
0.8 |
NG |
P > 0.01 |
|||
Kidney |
7 |
1.1 |
NG |
P > 0.01 |
|||
Skin melanoma |
8 |
1.2 |
NG |
P > 0.01 |
|||
Cervix/uterus |
162 |
1.3 |
[1.1-1.5] |
||||
McLaughlin |
Male printing 1961-79 |
Printing industry |
Skin melanoma |
91 |
1.4 |
[1.1-1.7] |
Morbidity |
Etal. (1988) |
Workers at 1960 |
Newspaper printing industry |
39 |
1.9 |
[I, 1-1.7] |
||
Sweden |
Census; |
Newspaper publishing industry |
7 |
3.1 |
|1.2-6.4| |
||
91 melanomas |
Typographets in newspaper printing industry Machine repairers in newspaper printing industry Journalists/editors in newspaper printing industry Business/executives in newspaper printing industry |
19 2 16 |
2.0 14.5 2.4 9,1 |
[1.2-3.1] [1.6-52.3] [1.4-3.9] [2.9-21.2] |
(continues,/ |
Reference, country |
Study subjects |
Period of follow-up |
Occupation/exposure |
Cancer site/ cause of death |
No. Obs |
RR |
95% Cl |
Aronson and |
242 196 women |
1965-79 |
Printing and publishing |
Breast |
11 |
2.2 |
1.1-3.9 |
Howe |
Identified through |
Industry |
|||||
(1994) |
Employment survey |
||||||
Canada |
|||||||
Costa et al. |
1981 population |
1981-89 |
Printing and publishing |
Pleura |
2 |
6.0 |
0.7-22 |
(1995) |
Census of Turin, |
Industry (M) |
|||||
Italy |
Italy, residents; |
Colon |
7 |
2.1 |
0.9-4.4 |
||
10 798 deaths |
|||||||
Lung |
22 |
1.1 |
[0.7-1.71 |
||||
Among persons |
|||||||
Employed |
Urinary bladder |
2 |
1.0 |
[0.1-3.6] |
|||
Haematopoietic |
7 |
1.6 |
0.6-3.3 |
||||
Printing and publishing |
Lung |
3 |
2.6 |
0.5-7.6 |
|||
Industry (F) |
Colon |
2 |
2.7 |
0.3-9.7 |
|||
Ovarian |
3 |
3.2 |
0.6-9.3 |
||||
Haematopoietic |
2 |
2.0 |
0.2-7.2 |
||||
Printers (M) |
Liver |
3 |
1.7 |
0.3-5.0 |
|||
Colon |
3 |
1.8 |
0.4-5.3 |
||||
Multiple myeloma |
2 |
[9.7] |
[1.1-33.1] |
||||
Lung |
12 |
1.2 |
[0.6-2.1] |
||||
Urinary bladder |
0 |
— |
— |
||||
Costa et al. |
.1981 population |
1981-82 |
Printing and publishing |
Kidney |
3 |
4.8 |
1,7-13.4 |
(1995) |
Census of Italian |
Industry (M) |
|||||
Italy |
Residents; |
||||||
15 734 deaths |
|||||||
Among persons |
|||||||
Employed |
|||||||
Lung |
11 |
1.1 |
[0.8-1.4] |
||||
Urinary bladder |
N Z. |
2.9 |
[0.8-11.1] |
Comments |
Mortality; other sites not significantly elevated Mortality |
244 |
Mortality |
L’ukka la «1995} Finland |
Morbidity |
1970 population 19/1-83 Printing occupa- census tions (M)
47 178 men,
46 853 women
Printing occupations (F)
Printers (F)
Printers (M)
Lithographers
Colon |
16 |
2.2 |
1.2-35. |
Lung |
50 |
0.8 |
0.6-1.1 |
Colon |
10 |
1.4 |
0.7-2.5 |
Lung |
12 |
1.8 |
0.9-3.2 |
Breast |
74 |
1.4 |
1.1-1.8 |
Ovarian |
30 |
2.2 |
1.5-3.1 |
Skin melanoma |
5 |
1.1 |
0.3-2.5 |
Skin melanoma |
7 |
1.1 |
0.5-2.4 |
Urinary bladder |
9 |
1.1 |
0.5-2.0 |
Leukemia |
2 |
0.4 |
0.1-1.4 |
Lung |
19 |
1.1 |
0.7-1.7 |
Skin basal-cell |
4 |
4.4 |
1.2-11.2 |
Carcinoma |
RR, relative risk estimated by SMR (for mortality) or SIR (for morbidity); M, male; F, female; NG not given.
International Agency for Research on Cancer (1996) “Printing processes and printing inks, carbon black and some nitro compounds”. IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 65, pp. 67-70. International Agency for REsearch on Cancer, Lyon, France.
No. of exposed
|
Reference, |
No. of exposed |
Odds |
|||||
Country |
Type of controls |
Exposure |
Sex |
Cases/controls |
Ratio |
95% Cl |
Comments |
Coggon et al.-® |
Deaths from other |
Printing inks |
M |
28/36 |
1.6 |
0.9-2.7 |
Job exposure matrix |
(1984) |
Causes |
Printing inks (high exposure) |
M |
9/9 |
2.0 |
0,8-5.0 |
Applied to occupa |
United Kingdom |
Tions recorded on death certificates; age <40 years, cases and controls |
||||||
Schoenberg et al.31 |
Population-based |
Printing workers >10 years |
M |
20/11 |
2.5 |
1.0-6.1 |
Adjusted for smoking |
USA |
M |
7/1 |
8.4 |
NG |
(p.20,05, crude) |
||
Printing industry |
M |
37/31 |
1.3 |
0.8-2.3 |
Adjusted for smoking |
||
Benhamou et al.~i2 |
Hospital-based, non |
Printers and related |
M |
32/51 |
1.2 |
0.7-1.9 |
Matched for sex, age at |
France |
Tobacco related diseases |
Workers |
Diagnosis, hospital, interviewer; adjusted for smoking |
||||
Hoar Zahm et al.53 |
Selected cancer sites |
Printing occupations |
M |
21/41 |
1.1 |
0.6-1.9 |
Adjusted for age, smoking |
USA |
7/[4] (adenocarci Noma) |
1.8 |
0.7-4.2 |
Occupations unknown for about half of cases and controls |
|||
Siemiatycki54 |
Hospital-based, |
Printing and publishing |
M |
35/NG |
2.0 |
[1.2-3.5] |
Smoking-adjusted |
(1991) |
Other cancers |
Industry |
|||||
(Canada) |
Printers |
M |
26/NG |
2.1 |
[1.1-4.1] |
Smoking-adjusted |
|
Printers (>10 years) |
M |
13/NG |
1.7 |
[0.7—4.1 ] |
Smoking-adjusted |
||
Printing process workers |
M |
15/NG |
3.1 |
[1.1-8.7] |
Smoking- ad j usted |
||
M |
6/NG (adenocarci |
7.0 |
[1.8-27.9] |
S m oking — a dj usted |
|||
Inks (any) |
M |
Noma ) |
1.6 |
[1,0-2.7] |
Smoking-adjusted |
||
Inks (substantial) |
M |
37/NG 18/NG |
1,5 |
(0.7-3.11 |
Smoking-adjusted |
Case-control Studies
In case-control studies, only one disease can be investigated. The cases include all patients with a certain disease observed in a hospital, city, or a larger area in a given period of time. Their exposure histories are compared with those of the controls. Thus, several exposures can be investigated. The exposure data are not very accurate because they are obtained by interview. Especially in cases of serious diseases, patients are often desperate to seek some reason for their disease. Therefore, patients of some other disease are usually employed as controls to avoid this information bias. The selection of controls is a crucial but extremely difficult task. Since factors such as age, sex, smoking, living habits, and place of abode are known to be risk factors for several diseases, the effects of these confounding factors are eliminated b matching. However, overmatching should also be avoided. Odds ratio (see Table 5.8b, c) is used to express how often the cases have been exposed to various exposures compared to controls. Case-control studies are common because they are inexpensive and relatively easy to perform. If the disease studied is rare, this approach is also the only practical alternative.12
5.3.1.3 Classifications of Toxicology
The word toxicology originates from the Greek word toxicon, which means arrow. In ancient times, arrows were dipped into plant poisons to increase their lethality in hunting. Today, toxicology refers to that scientific discipline that explores the deleterious effects of chemicals or of physical or biological factors on living organisms. Toxicology also explores the mechanisms whereby chemicals, or physical or biological factors induce their harmful effects in the organism.
There are several definitions and classifications of toxicology. One classification is based on the target organs which are harmfully affected by chemicals. Hence, there are terms such as neurotoxicology, liver or hepatic toxicology, kidney or renal toxicology, and toxicology of the eye (ocular toxicology). Inhalational toxicology emphasizes the importance of the lungs as the target organ of chemicals. In addition to these descriptive classifications, toxicology can be divided into mechanistic toxicology, conducted mainly in university and governmental research institutions, and descriptive or regulatory toxicology, which is required for classification and labelling of chemicals for registration purposes. Even if mechanistic toxicology is essential for understanding how chemicals and other factors induce their toxic effects, descriptive toxicology is also important in characterizing the properties of a chemical compound. Descriptive toxicology is a prerequisite for regulatory purposes and risk assessment. When the qualitative requirements for risk assessment increase, the importance of mechanistic information on chemicals in risk assessment wilt also increase.
Toxicology can also be divided into different classes based on the goals it serves. Clinical toxicology explores ways of treating poisoned patients, and also aims to develop quick methods to diagnose poisonings. Forensic toxicology is the science involved in detecting the role of poisons in fatalities. Environmental toxicology assesses the importance of environmental pollution and the effects of exposure through various environmental compartments on human health. Ecotoxicology is interested in the effects of environmental chemicals on
.3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS HHH1 TABLE 5.9 Classifications of Toxicology
|
Animals such as fish, insects, birds, and other wild animals. Industrial or occupational toxicology aims to study the effects of chemicals on workers exposed in an occupational environment (see Table 5.9).
Toxicology often provides the basis for a number of regulations aimed at protecting workers from potentially harmful effects. Today, more than ever before, toxicology has a preventive function that provides information on chemicals that can be used safely. It is difficult to imagine occupational or other safety regulations without a major input from toxicology.
The main role of toxicology in the industrial setting originates from its ability to identify harmful chemicals and other hazards in advance. After toxi — cological research has identified exposure-effects relationships for different chemicals, occupational exposure limits (OELs) for various industrial chemicals can be established. Subsequently, workers can be protected against excessive exposures by measuring the exposure and ensuring that the OELs are not violated; ventilation engineers and occupational hygienists are the key persons in this field. Careful planning and design can ensure that most workers can be protected, nevertheless the most sensitive individuals may still react to exposure levels that are below the acceptable exposure limits. These relationships also indicate the close relationship between industrial toxicology and industrial hygiene. Without a broad knowledge of the toxicological characteristics of chemicals, industrial hygiene is more or less irrelevant. On the other hand, without industrial hygiene, toxicology would be helpless in protecting the workers against chemical hazards.
5.3.1.4 Industrial Toxicology, Hygiene, and Occupational Medicine
Industrial toxicology, industrial hygiene, and occupational medicine all have a common goal: to protect workers from occupational hazards in the workplace. The goal of toxicological research is to protect the worker by characterizing the biological effects of chemicals and by identifying the hazardous agents, whereas the goal of occupational hygiene is to protect workers by improving the occupational environment. The goal of occupational medicine, in turn, is to protect workers’ health by identifying early signs of harmful effects, and to diagnose and treat occupation-related diseases. In
Many cases, reduction of exposure will suffice to prevent many occupation — related diseases after the first symptoms, but the exposure may also need ro be stopped completely. However, before such radical measures can be taken, the association between the exposure and the disease has to be established, i. e., the occupational nature of the disease needs to be demonstrated. Therefore, occupational medicine relies on toxicological and occupational hygienic knowledge in solving occupational health problems. However, the scope of occupational medicine is much wTider than simply examining chemical-induced toxicity, as it covers a wide area of interests such as occupational ergonomics and psychophysiological factors in the occupational setting.35
Poisoning Incidents in the Workplace
The hazards of chemicals are commonly detected in the workplace first, because exposure levels there are higher than in the general environment. In addition, the exposed population is well known, which allows early detection of the association between deleterious health effects and the exposure. The toxic effects of some chemicals, such as mercurv compounds and soot, have been known already for centuries. Alreadv at the end of the eighteenth century, small boys who were employed to climb up the inside of chimneys to clean them suffered from a cancer of the scrotum due to exposure to soot. This was the first occupational cancer ever identified. In the viscose industry, exposure to carbon disulfide was already known to cause psychoses among exposed workers during the nineteenth century. As late as the 1970s, vinyl chloride was found to induce angiosarcoma of the liver, a tumor that was practically unknown in other instances.36
Even in the Nordic countries, exposure to carbon disulfide still caused severe central nervous effects among exposed workers during the late 1960s and early 1970s, and exposure to lead caused several lead poisonings at the same time. Exposure to asbestos remained a major health hazard until the 1970s. The use of asbestos is nowadays strictly controlled and it has been banned in many countries. Nevertheless, it continues to be an important occupational health problem because of the long latency period of asbestos for causing lung cancer and mesothelioma, a time period of 20^10 years. In addition, there are large amounts of asbestos remaining in buildings, and renovation of old buildings will pose a health risk to workers for a long time to come.37
Many very hazardous solvents, such as benzene and carbon tetrachloride, were widely used until the 1970s. The situation was very similar for the use of pesticides. Among the toxic pesticides that were still in wide use 20 years ago were chlorophenols, DDT, lindane, and arsenic salts, all of which are classified as human carcinogens as well as being acutely toxic.4’3K Fortunately, use of these kinds of very toxic chemicals is now limited in the industrialized world. However, because the number of chemicals used in various industries continues to increase, the risks of long-term health hazards due to long-term exposure to low concentrations of chemicals continues to be a problem in the workplace.
Association of Industrial Activity and Poisonings in the General Environment
The harmful effects of industrial emissions are not confined to the workers but extend beyond the plant boundary line. Chemically-induced diseases among workers exposed to industrial chemicals are a warning sign of the risks to which a larger population is also being exposed; usually the chemical hazards are in principle similar in the occupational and general environment. However, occasionally environmental exposures can be qualitatively different from the occupational environment and may also cause deleterious health effects in the general population.59’40
Since the general population is much larger than the occupationally exposed worker groups, and also includes very sensitive individuals, some deleterious effects have been detected only in the general population. Urban air pollution is a good example. In the 1930s, an air pollution incident in the valley of the River Maas in Belgium was responsible for the deaths of tens of individuals due to increased concentrations of coal dust and sulfur dioxide in the ambient air. At that time, it was already predicted that this could be a harbinger of future catastrophes in a major city like London, and, indeed, in 1952, a dramatic increase of concentrations in small coal particles and sulfur dioxide took place during weather inversion in the London metropolitan area. In consequence, an excess mortality of more than 4000 individuals occurred during a few days. Similar though less severe smogs (a fog caused by air pollution) took place in the late 1950s. Subsequently the use of coal was prohibited in London and today the air quality in the city is much better than it was 40 years ago. In addition to this classic kind of smog, photochemical smog, consisting of nitrous oxides and ozone and their reaction products with hydrocarbons, is encountered in warm and sunny areas where there is major traffic-related pollution. A model area for such a situation is Los Angeles, California, where the air quality is a continuous concern.41
The emphasis on air pollution in different parts of the world has led to marked improvements in air quality. However, there are several metropolitan areas in the world where the air pollution situation is still deteriorating. Examples of such areas are Mexico City, Mexico, New Delhi, India, Cairo, Egypt, and Sao Paulo, Brazil. Most of these badly polluted areas are in developing countries where resources for improving the situation are limited. Thus, these problems are difficult to solve (see Fig. 5.30).41
Recently, much emphasis has been put on the harmful effects of small particles, i. e., particulate matter (PM), on human health. A number of standards have been established to characterize the PM fractions in the air and their effects on human health. A widely used PM standard in force in both Europe and the United States is based on the mass concentration of particles with a diameter of 10 |xm or less (PM10). However, recently the U. S. Environmental Protection Agency (EPA) proposed a new standard that is based on the aerodynamic diameter of 2.5 jjim particles. This new standard emphasizes the significant impact of small particles on human health, especially on the respiratory and cardiovascular systems.41,42
It has been known for years that professional bus and truck drivers as well as railroad workers suffer a larger than average risk of lung cancer because of
Mega-cities
0 200 400 600 800 1000 1200 ■■ FIGURE 5.30 Comparison of ambient levels of I h maximum ozone, annual average of total suspended particulate matter (TSP), and sulfur dioxide in selected cities from around the world to illustrate the variation in these levels from country to country with respect to the United States. (Reproduced from the National Air Quality and Emission Trends Report ( 1992), with permission.]»1 |
Bangkok Beijing Bombay Buenos Aires Cairo Calcutta Delhi Jakarta Karachi London Los Angeles Manila Mexico City Moscow New York Rio de Janeiro Sao Paolo Seoul Shanghai Tokyo
Exposure to gas engine, especially diesel engine, exhausts. These individuals are also at a larger than average risk of sudden death due to myocardial infarction, cardiovascular disease, and pulmonary disease. Several studies from the U. S. and Europe have demonstrated that exposure to inhalable particles, especially those generated by traffic and energy production, cause a one to five percent increased risk of mortality among the general population. At the European level, this would represent 50 000 to 100 000 additional deaths annually.43,44 It is probable that the previous examples of increased mortality during historical air pollution episodes were largely due to exposure to small particles. Unfortunately, no clear conclusions can yet be made concerning occupational dust exposure in general.
The term risk has wide implications. It is used to characterize difficulties in predicting changes in the currency markets and to indicate the probability of potential financial losses due to such changes. A surgeon prior to a major operation also needs to evaluate the risks to the patient, not only due to the disease, but also risks associated with the operation itself and the anesthesia. Car drivers seldom consider the risk of a traffic accident when starting a car even though the risk of a fatal car accident is many rimes greater than the calculated risks associated with exposure to chemicals. Another example, widely discussed in the media, is the comparison of risks from energy production by fossil fuels and nuclear energy. This comparison has proven to be extremely difficult due to a number of philosophical aspects. We can calculate with some degree of certainty the risks involved in the production of energy with
Fossil fuels. There are major risks in mining or oil drilling, during the transportation of the fuel, and due to the extensive emissions emanating from the combustion of the fuel. In Europe, annual loss of life due to energy production utilizing fossil fuels, and due to traffic exhaust, is close to 100 000. The verifiable health hazards due to nuclear energy are only a small fraction of the losses due to the use of fossil fuels. However, the potential risk due to a nuclear accident raises alarm in individuals, because the true risk due to nuclear energy cannot be calculated. Even if the accident probability is small, the losses due to even one incident may be catastrophic. This is well illustrated by the accident in Chernobyl in 1986.4j’46
If one is to estimate the potential hazards of some chemicals prior to their release to the market, the chemicals must be tested for their toxicity in experimental animals. Animals are exposed to high doses of chemicals to avoid the use of large numbers of animals. When the results of animal experiments are applied to humans, several assumptions have to be made, including (1) that animals are a good model to predict human hazards caused by chemicals, and (2) that large doses of chemicals used in studies utilizing small groups of experimental animals cause similar effects to what would be seen in humans though at a lower frequency or with a milder change in functions of target organs. Toxic effects of chemicals may, however, be quite different in rodents than in humans. For example, guinea pigs tolerate the effects of strychnine rather well, in contrast to humans. For organ toxicity (neurotoxicity, liver toxicity, kidney toxicity) endpoints, safety factors can be used for assessing safe levels for humans {see below). Dose-responses are regularly used to delineate the toxicological characteristics of chemical compounds, and to make comparisons of effects between species.1’47
In most cases, experimental animal studies are used to define the so-called no-observable-adverse-effect level (NOAEL), i. e., the lowest dose that does not cause an adverse effect in experimental animals. This dose is then divided by a safety factor of 100, ten for interspecies differences between rodents and humans and ten for intraspecies differences between humans, to calculate the dose (mg/kg) which is considered to be safe for humans. This approach contains the assumption that there is a safe dose below which a chemical does not cause harmful effects on humans (for the safety factor of 100, see Fig. 5.31). This assumption of a safe threshold dose is used for most endpoints of deterministic toxicology, i. e., organ toxicology. However, whether in fact there can be any safe dose for carcinogens, especially for genotoxic carcinogens, has been challenged, and the linear extrapolation models widely used in carcinogenic risk assessment do not utilize safety factors. However, this approach has also been recently challenged because throughout biology, one does not find effects without any threshold, and because it neglects biological defence mechanisms present within cells. The thresholds may, however, be so low in some instances that the arguments are purely theoretical. However, they have important implications for risk assessment.47’49 Furthermore, one can argue that none of the toxicological endpoints, whether deterministic (organ toxicity) or stochastic (cancer) in nature, have a threshold. This may be true conceptually, and it is especially true experimentally because in most cases determination of a true threshold is beyond the limit of detection of the experimental approach.
Interspecies |
Interindividual |
|
Differences |
Differences |
|
10-fold |
10-fold |
100-fold uncertainty factor |
Toxico — dynamics 100.4 |
Toxico Kinetics 100.6 (4.0) |
T oxico — dynamics ‘ lO0-5 (3.2) |
Toxico Kinetics LO«-‘ (3.2! |
(2.5)
FIGURE 5.31 Subdivision of the 100-fold uncertainty factor showing the relationship between the use of uncertainty factors (above the dashed line) and proposed subdivisions based on toxicokinetics and toxicodynamics. Actual data should be used to replace the default values if available.48
Usually risk assessment procedure, discussed in more detail later (see Chapter 6), is divided into four different stages or steps (see Fig. 5.32):49
1. Hazard identification through animal experiments, epidemiological studies, or structure activity analyses
2. Hazard characterization, or dose-response characterization, by using experimental animals to reveal target organs and toxic doses, and the shape of the dose-response curve
3. Exposure assessment to reveal the exposure of different groups of people, and to compare their exposure levels to the doses that cause harmful effects in humans as shown in epidemiological studies, or to doses that cause toxic effects in experimental animals
4. Risk assessment, a synthesis of the preceding three steps, which aims to assess both qualitatively and quantitatively the risks induced by a chemical at a given or at different exposure levels.
This step utilizes either a safety factor approach or various extrapolation models.
Based on the results of risk assessment, decision makers have to attempt to manage risks, e. g., by determining various exposure limits to protect individuals against deleterious effects of chemical exposures. This kind of procedure is commonly used for determining acceptable daily intake values (ADIs)49 for contaminants in foods and acceptable operator exposure level (AOELs) for pesticides. Even though the results obtained in experimental animal tests are part of the basic data on which the OELs have been based, the levels result from consideration of many other aspects, especially epidemiological data. In addition, these decisions take into consideration economic and political consequences of the decisions, as well as perception of various risks by the general public. Furthermore, properties such as strong odor or irritation influence the levels of OELs. It needs to be kept in mind that even though risk assessment of exposures
Research, Risk assessment Risk managernnet
Toxicity assessment: hazard identification and dose-response assessment |
A |
|
![]() |
|
||
|
||||
|
||||
|
||||
|
||||
|
|||
|
|
||
FIGURE 5.32 Elements of risk assessment and risk management.49(used with permission.)
To single chemicals is still far from complete, much greater difficulties are encountered in assessing the risks of multiple exposures.
Posted in INDUSTRIAL VENTILATION DESIGN GUIDEBOOK