Exposures In Occupational Settings Research Articles

Toxicity and Carcinogenicity of Chromium Compounds in Humans

Chromium is a human carcinogen primarily by inhalation exposure in occupational settings. Although lung cancer has been established as a consequence of hexavalent chromium exposure in smokers and nonsmokers, some cancers of other tissues of the gastrointestinal and central nervous systems have also been noted. Except for a few reports from China, little is known about the health risks of environmental exposures to chromium. Likewise, there has been a lack of epidemiological studies of human exposure to hexavalent Cr by drinking water or ingestion, and it has been suggested that humans can perhaps tolerate hexavalent Cr at higher levels than the current drinking water standard of 50 ppb. This review highlights the most recent data on the induction of skin tumors in mice by chronic drinking-water exposure to hexavalent chromium in combination with solar ultraviolet light. This experimental system represents an important new animal model for chromate-induced cancers by ingestion of drinking water, and it suggests by extrapolation that chromate can likely be considered a human carcinogen by ingestion as well. The potential use of this animal model for future risk assessment is discussed.

Local effects in the respiratory tract: relevance of subjectively measured irritation for setting occupational exposure limits

Chemosensory effects of stimulation by a chemical can either be irritating (trigeminal stimulation) or odorous (olfactory stimulation) or both. For odorous irritants, a clear-cut distinction between odour and irritation is difficult to make. The differences in the lowest concentration found to be irritating to the respiratory tract in humans when compared to experimental animals has brought much debate in the process of setting occupational exposure limits (OELs) for such chemicals. In this paper it will be discussed as to how far subjectively measured sensory irritation threshold levels can be used to establish OELs. Data on respiratory irritation of four odorous irritants were retrieved from public literature and discussed, viz. acetone, formaldehyde, furfural and sulphur dioxide. Objective measures of irritation yielded results that differed from subjective evaluations. Important factors modulating the reported levels of irritation and health symptoms include the perception of odour intensity, exposure history and the individual's bias to report irritation on the basis of his/her prejudice or knowledge of the compound. Subjective measures alone are less appropriate for establishing sensory irritation thresholds of odorous irritants and are, therefore, less suitable to establish OELs without supporting evidence. Objectively measured irritation in humans, the Alarie assay (an experimental animal test assessing the concentration that results in a 50% reduction of the breathing frequency) and repeated exposure studies in animals may be of help to study objective irritation. If subjective measurements are used to study sensory irritation, the study design should at least include: measurement of both incidence and severity determined at several concentrations, an appropriate (0 ppm) control condition, preferably a non-irritant odorant control exposure, validated questionnaires and correct concentration measurements.

Cadmium and Kidneys: Low-Level Exposure and Effects in Women

Widespread exposure to the heavy metal cadmium occurs through both natural and industry-related sources. The general population is likely to encounter low-level chronic exposure through smoking and from dietary sources, particularly shellfish, grains, and vegetables. In 1999 an ongoing population-based Swedish study, Women’s Health in the Lund Area, was expanded to include low-level cadmium exposure. Analysis of the data collected now reveals a small but significant kidney response to low-level cadmium exposure [EHP 113:1627–1631]. This suggests that low-level cadmium exposure may pose a significant public health risk. Owing to extremely slow excretion, cadmium accumulates in the body, especially in the kidneys. Kidney damage is the primary consequence, but most toxicity data are from exposures in occupational settings or severely polluted areas. The effects of low-level exposure are less certain. A primary function of the kidney is to filter excess water and metabolic by-products from the blood for urinary excretion. This filtration occurs in more than 1 million nephrons, each of which contains a blood capillary (the glomerulus) intertwined with a urine-collecting tubule. In the current study, researchers assessed glomerular and tubular fitness by measuring kidney function markers in blood and urine, respectively. Blood testing also revealed ongoing cadmium exposure, and urinalysis indicated cadmium body burden. The team analyzed data, including blood and urine samples, collected from 820 women aged 54–63 years. Blood levels of creatinine and cystatin C were measured in 742 participants to calculate glomerular function. Urinary concentrations of calcium, human complex-forming protein, and N-acetyl-β-d-glucosaminidase—all markers of tubule function—were available for 813 women. The researchers additionally collected data on medications taken, smoking history, lead exposure, and incidence of diabetes and hypertension to control for potential confounding factors. Cadmium concentrations were similar or slightly higher compared with previous data from Sweden and much lower than concentrations reported for populations in highly polluted areas in Europe and Japan. Current or former smokers had cadmium concentrations that were 90% higher in blood and 40% higher in urine than concentrations measured in participants who never smoked. Consequently, multivariate analyses were conducted on data from all participants as one group and from those who had never smoked as another group. Cadmium concentrations were positively associated with the tubular function markers, indicating some damage to the tubules. Increased cadmium was also associated with decreased creatinine clearance, reflecting a reduced glomerular filtration rate. The lowest-observed-effect level for increased tubular markers was a mean urinary cadmium concentration of 0.6 microgram per liter, which is lower than previously reported. A reduction in glomerular filtration rate was associated with a minimum mean urinary cadmium concentration of 0.86 microgram per liter. The researchers speculate that effect levels might be even lower for people with diabetes, a disease carrying high risk of kidney damage similar to that caused by cadmium exposure. Although the effects of low-level cadmium exposure are clinically minor, they should be viewed as early indicators of potential severe health effects, according to the researchers. Given the size of the exposed population, there may be a significant public health risk, and efforts beyond smoking cessation programs are needed to reduce exposure.

Estimating the Number of Asbestos-related Lung Cancer Deaths in Great Britain from 1980 to 2000

Inhalation of asbestos fibres is known to cause two main kinds of cancer-mesothelioma and lung cancer. While the vast majority of mesothelioma cases are generally accepted as being caused by asbestos, the proportion of asbestos-related lung cancers is less clear and cannot be determined directly because cases are not clinically distinguishable from those due to other causes. The aim of this study was to estimate the number of asbestos-related lung cancers among males by modelling their relative lung cancer mortality among occupations within Great Britain in terms of smoking habits, mesothelioma mortality (as an index of asbestos exposure) and occupation type (as a proxy for socio-economic factors). Proportional mortality ratios for lung cancer and mesothelioma for the 20-year period from 1980 to 2000 (excluding 1981) were calculated for occupational groups. Smoking indicators were developed from three General Household Surveys carried out during the 1980s and 1990s. Poisson regression models were used to estimate the number of asbestos-related lung cancers by estimating the number of lung cancer deaths in each occupation assuming no asbestos exposure and subtracting this from the actual predicted number of lung cancer deaths. The effect of asbestos exposure in predicting lung cancer mortality was weak in comparison to smoking habits and occupation type. The proportion of current smokers in occupational groups and average age at which they started smoking were particularly important factors. Our estimate of the number of asbestos-related lung cancers was between two-thirds and one death for every mesothelioma death: equivalent to between 11 500 and 16 500 deaths during the time period studied. Asbestos-related lung cancer is likely to have accounted for 2-3% of all lung cancer deaths among males in Great Britain over the last two decades of the 20th century. Asbestos-related lung cancers are likely to remain an important component of the total number of lung cancer deaths in the future as part of the legacy of past asbestos exposures in occupational settings.

Evaluating the human response to chemicals: odor, irritation and non-sensory factors

Although airborne chemicals can directly elicit adverse reactions via stimulation of the olfactory and trigeminal nerves, such as sensory irritation of the mucous membranes of the eyes, nose and throat, an individual's subjective experience is often the result of a complex sequence of events involving those sensory, physiological signals and psychological processes involved in perception, memory and judgment. To evaluate the contribution of these processes, an information-processing model of chemosensory perception is introduced. The model incorporates (1) the perception of odor and trigeminal irritation, and accompanying physiological and somatic changes that follow directly from the encounter with volatile organic compounds (VOCs) in the environment (bottom-up processing), and (2) any physiological/ somatic changes and subjective experiences of irritancy that are influenced by cognitive processes that have been primed by the perception of odor (top-down processing). The model is illustrated with data from our laboratory, and its utility in the context of setting occupational exposure limits is discussed.

Study on OELs for enzyme-containing detergent in China.

This study is aimed at setting occupational exposure levels for total detergent dust and enzymes in detergent industries. The study population consisted of 795 workers from four enzyme-containing detergent manufacturing plants (A1, A2, B1 and B2), and 156 control workers from an electronic assembly factory. Work environment monitoring was conducted using high volume of air sampler fro measuring the concentration of total dust (mg/m3), and analyzing the level of enzyme (ng/m3) by ELISA method. A standard questionnaires, pulmonary function test, and skin prick test are used to assess health effects. The levels of detergent total dust varied from 0.2 mg/m3 to 12.54 mg/m3. For enzyme levels, in A1, B1 and B2, the concentration ranged from non-detectable to 9.92 ng/m3 and in A2, the concentration was analyzed by enzyme activity methods and was expressed as Gu/m3 (1 Gu/m3 = 16 ng/m3). The concentration is between 0.16-31.36 ng/m3. Non-specific irritation rates in exposed workers were significantly higher than that in controls. Based on the data collected from A1, B1 and control plants, 95% benchmark dose lower bound were calculated as 1.17 mg/m3. The difference of pulmonary function between exposed workers and controls is not significant. The results of SPT showed that neither Savinase- nor Alcalase-induced sensitization was found in controls. The prevalence rates of sensitization for Savinase and Alcalase were ranged between 3.2% and 31% in all enzyme-containing detergent manufacturers investigated. No case of occupational asthma was observed. For total dust, 1 mg/m3 is suggested as permissible concentration-time weighted average (PC-TWA), and 2 mg/m3 as permissible concentration-short term exposure limit (PC-STEL). For the enzyme Subtilisins, 15 ng/m3 is suggested as PC-TWA, and 30 ng/m3 as PC-STEL.

Dermal exposure assessment to benzene and toluene using charcoal cloth pads

Charcoal cloth pads have been used to assess volatile chemicals on the skin in a laboratory setting; however, they have not yet been applied to measure dermal exposure in occupational settings. This study aimed at evaluating whether charcoal pads can be used to assess dermal exposure to benzene and toluene in workers of a petrochemical plant. Inhalation and dermal exposure levels to benzene and toluene were assessed for workers of a petrochemical plant performing different jobs. Benzene uptake was assessed by determining S-phenylmercapturic acid in workers' urine samples. Dermal exposure levels on the charcoal pads were adjusted for ambient air levels of benzene and toluene by subtracting the amount of benzene or toluene measured in personal air from the amount of benzene or toluene measured on the charcoal pad. In general, measured external and internal exposure levels were low. The estimated contribution of the dermal route to internal benzene exposure levels was less than 0.06% for all jobs. Toluene personal air concentrations and benzene and toluene dermal exposure levels differed statistically significantly between job titles. For benzene, differences between jobs were larger for adjusted dermal exposures (maximum 17-fold, P = 0.02) than for inhalation exposures (maximum two-fold, P = 0.08). Also for toluene, although less clear, differences between jobs were larger for adjusted dermal exposures (maximum 23-fold, P = 0.01) as compared to inhalation exposures (maximum 10-fold, P = 0.01). Charcoal pads appeared to measure dermal exposures to benzene and toluene in addition to ambient air levels. Future studies applying charcoal cloth pads for the dermal exposure assessment at workplaces with higher dermal exposure to organic solvents may provide more insight into the biological relevance of dermal exposure levels measured by charcoal cloth pads. In addition, the design of the dermal sampler might be improved by configuring a dermal sampler, where part of the sampler is protected against direct contact and splashes, but still permeable for the gas phase. This design would most likely result in a better ability to correct for airborne concentrations at a given body location.

The epidemiology of laryngeal cancer in Brazil

The city of São Paulo exhibits one of the highest incidences of laryngeal cancer in world and Brazil presents remarkable occurrence, compared with other Latin American countries. Around 8,000 new cases and 3,000 deaths by laryngeal cancer occur annually in the Brazilian population. In the city of São Paulo, incidence rates for laryngeal cancer among males have been decreasing since the late 1980s while, among females, the rates have shown a stable trend. This phenomenon is probably the expression of changes in gender behavior related to tobacco smoking. Several risk factors are involved in the genesis of laryngeal cancer. The most important are tobacco smoking and alcohol intake, but occupational hazards have also been associated with the disease, such as asbestos, strong inorganic acids, cement dust and free crystalline silica. Additionally, salted meat and total fat intake have been linked to elevated risk of laryngeal cancer. Conversely, several studies have confirmed that fruits, raw leaf vegetables and legumes protect against this cancer. Some researchers have postulated a possible association between laryngeal squamous cell carcinoma and human papilloma virus (HPV), but this is not universally accepted. Gastroesophageal reflux disease is weakly, but consistently correlated with laryngeal cancer. Familial cancer clusters, particularly of head and neck tumors, seem to increase the risk of laryngeal cancer. Some genetic polymorphisms, such as of genes that code for xenobiotic-metabolizing enzymes, have shown elevated risk for laryngeal cancer according to recent studies. Public health policies regarding the control of tobacco smoking and alcohol consumption, and also surveillance of carcinogen exposure in occupational settings, could have an impact on laryngeal cancer. No proposals for screening have been recommended for laryngeal cancer, but one diagnostic goal should be to avoid treatment delay when suspected symptoms have been observed.

Carcinogenic and systemic health effects associated with arsenic exposure--a critical review.

Arsenic and arsenic containing compounds are human carcinogens. Exposure to arsenic occurs occupationally in several industries, including mining, pesticide, pharmaceutical, glass and microelectronics, as well as environmentally from both industrial and natural sources. Inhalation is the principal route of arsenic exposure in occupational settings, while ingestion of contaminated drinking water is the predominant source of significant environmental exposure globally. Drinking water contamination by arsenic remains a major public health problem. Acute and chronic arsenic exposure via drinking water has been reported in many countries of the world, where a large proportion of drinking water is contaminated with high concentrations of arsenic. General health effects that are associated with arsenic exposure include cardiovascular and peripheral vascular disease, developmental anomalies, neurologic and neurobehavioural disorders, diabetes, hearing loss, portal fibrosis, hematologic disorders (anemia, leukopenia and eosinophilia) and multiple cancers: significantly higher standardized mortality rates and cumulative mortality rates for cancers of the skin, lung, liver, urinary bladder, kidney, and colon in many areas of arsenic pollution. Although several epidemiological studies have documented the sources of exposure and the global impact of arsenic contamination, the mechanisms by which arsenic induces health effects, including cancer, are not well characterized. Further research is needed to provide a better understanding of the pathobiology of arsenic-induced diseases and to better define the toxicologic pathology of arsenic in various organ systems. In this review, we provide and discuss the underlying pathology and nature of arsenic-induced lesions. Such information is critical for understanding the magnitude of health effects associated with arsenic exposure throughout the world.

An Analysis of Human Response to the Irritancy of Acetone Vapors

Studies on the irritative effects of acetone vapor in humans and experimental animals have revealed large differences in the lowest acetone concentration found to be irritative to the respiratory tract and eyes. This has brought on much confusion in the process of setting occupational exposure limits for acetone. A literature survey was carried out focusing on the differences in results between studies using subjective (neuro)behavioral methods (questionnaires) and studies using objective measurements to detect odor and irritation thresholds.A critical review of published studies revealed that the odor detection threshold of acetone ranges from about 20 to about 400 ppm. Loss of sensitivity due to adaptation and/or habituation to acetone odor may occur, as was shown in studies comparing workers previously exposed to acetone with previously unexposed subjects. It further appeared that the sensory irritation threshold of acetone lies between 10,000 and 40,000 ppm. Thus, the threshold for sensory irritation is much higher than the odor detection limit, a conclusion that is supported by observations in anosmics, showing a ten times higher irritation threshold level than the odor threshold found in normosmics. The two-times higher sensory irritation threshold observed in acetone-exposed workers compared with previously nonexposed controls can apart from adaptation be ascribed to habituation. An evaluation of studies on subjectively reported irritation at acetone concentrations <1000 ppm shows that perception of odor intensity, information bias, and exposure history (i.e., habituation) are confounding factors in the reporting of irritation thresholds and health symptoms.In conclusion, subjective measures alone are inappropriate for establishing sensory irritation effects and sensory irritation threshold levels of odorants such as acetone. Clearly, the sensory irritation threshold of acetone should be based on objective measurements.

Induction of DNA-strand breaks in human peripheral blood lymphocytes and A549 lung cells by sodium dichromate: association with 8-oxo-2-deoxyguanosine formation and inter-individual variability

Hexavalent chromium [Cr(VI)] is a genotoxic carcinogen for which inhalation is a major potential route of exposure in occupational settings. In the present study, the ability of sodium dichromate to cause DNA strand breaks in three populations of cells, human whole blood cells, isolated human peripheral blood lymphocytes and cultured A549 lung epithelial cells, was investigated. Treatment with non-cytotoxic concentrations of sodium dichromate (for 1 h) resulted in a concentration-dependent increase in the number of DNA strand breaks as measured by the Comet assay. The lowest concentrations of sodium dichromate that resulted in a statistically significant (P < 0.01) increase in the number of DNA strand breaks were 500, 50 and 10 microM, respectively, in these cells. The use of formamidopyrimidine glycosylase increased the sensitivity of detection of strand breaks in A549 cells 10-fold, suggesting a role for DNA base oxidation in the mechanism of dichromate-induced DNA strand breaks. In support of this hypothesis, immunocytochemistry indicated an elevation of 8-oxodeoxyguanosine in A549 cells treated with 10 and 500 microM sodium dichromate for 1 h. We also demonstrated 2.11- and 2.5-fold ranges in the level of control and dichromate (500 microM)-induced DNA strand breaks, respectively, in cells of whole blood within a group of healthy volunteers (n = 26). A statistically significant (P < 0.001) positive Pearson's correlation (r = 0.606) was found between control and treated levels of DNA strand breaks, suggesting that factors responsible for relatively low levels of DNA strand breaks in untreated PBL may also offer protection against the formation of dichromate-induced DNA strand breaks.

Approach to setting occupational exposure limits for sensory irritants in The Netherlands.

This article describes how scientists in the Netherlands set occupational exposure limits (OELs) for sensory irritants. When they tackle this issue, a number of key questions need to be answered. For example, did the studies indeed measure sensory irritation and not cytotoxicity? When the irritant is an odorant, can interference of olfactory stimulation be excluded? In the case of subjective measurements, can psychological irritation be excluded? When adaptation is an issue, did the studies indeed measure adaptation and not habituation? When OELs are established in the Netherlands, each of these issues is carefully addressed before a value is suggested. When setting an OEL in the Netherlands, human data carry more weight than animal data of comparable quality. As in the United States, documentation for the recommended OEL is written and a discussion of all available relevant and reliable data culminating in the selection of the key study for deriving the health-based recommended occupational exposure limit is provided. Special effort is dedicated to reconciling differences between the animal and human data. If the toxicological database is considered to be inadequate, the committee acknowledges this limitation and will not recommend a limit value due to insufficient data.

The development of a new method to estimate total daily dose of pesticides in professional turf applicators following multiple and varied exposures in occupational settings.

The evaluation of absorbed dose of pesticides in humans requires a knowledge of the kinetics and dynamics of the compound. In some circumstances, data that allow for the estimation of dose may be available from human volunteer studies, although often, it will be based on results from animal studies. If human metabolism data are available, estimates of dose may be more accurate, but it should be recognized that pesticide exposure in an occupational setting may differ from that in a controlled laboratory study. In this study, data from previously published studies are used to evaluate the urinary excretion of 2,4-dichlorophenoxyacetic acid (2,4-D), following single dermal applications to human volunteers. These studies are evaluated with the objective of determining the best method of predicting total absorbed dose following multiple and varied exposures in occupational settings. Further, an alternative to laboratory-controlled human volunteer studies is presented. Data from a third previously published biological monitoring study on six professional pesticide applicators over a 2-week period were used to generate estimates of the urinary excretion of the pesticide 2,4-D that would result from a single dose. The method used to estimate the urinary excretion parameters is a variation of an overlay technique used in pharmacology, and may provide information on the kinetics of other pesticides when it is not possible to conduct human studies. The generated estimates of 24-h urinary excretion of 2,4-D over a 6-day period were remarkably similar to those obtained in controlled studies. Finally, a method was developed to use the generated estimates to determine total absorbed dose of pesticides for an independent group of 95 professional pesticide applicators. This method requires information on the amount of pesticide used for 6 days prior to the collection of two, 24-h urine samples.

An overview of setting occupational exposure limits (OELs) for pharmaceuticals

Introduction Occupational exposure limits (OELs) 1 for the protection of workers have been around at least since 1939 when the National (later changed to American) Conference of Governmental Industrial Hygienists (ACGIH) published its inaugural acceptable workplace exposure limits (now known as threshold limit values, or TLVs). In 1970, the U. S. Occupational Safety and Health Act incorporated by reference the 1968 ACGIH TLVs as enforceable limits. The Occupational Safety and Health Administration (OSHA) refers to these enforceable limits as permissible exposure limits (PELs).

International Occupational Exposure Standards: A Review and Commentary

This article is a report of work carried out during visits to Australia, Britain, Norway, and Russia for the purpose of becoming acquainted with the various processes of setting occupational exposure standards in those countries. The article reviews the processes by which occupational exposure standards are developed from country to country, examines the role of the occupational hygiene discipline in their development and implementation, and reflects on the complex philosophical and practical issues that surround them and the prospects for international harmonization.

International Occupational Exposure Standards: A Review and Commentary

This article is a report of work carried out during visits to Australia, Britain, Norway, and Russia for the purpose of becoming acquainted with the various processes of setting occupational exposure standards in those countries. The article reviews the processes by which occupational exposure standards are developed from country to country, examines the role of the occupational hygiene discipline in their development and implementation, and reflects on the complex philosophical and practical issues that surround them and the prospects for international harmonization.

Lung Pathology and Mineralogy Associated with High Pulmonary Burden of Metal Particles: Fe, Ti, Al and Cr In a Pneumoconiosis Database

The inhalation of respirable inorganic particles at low levels is a commonplace everyday occurrence. Typically, the types of particulates which are inhaled and variably retained in the lungs, are those commonly present in ambient aerosols. Much of the particulate matter is aeolian crustal material (deflationary soil) and anthropogenerated material (combustion emissions, construction products). This low or background level of exposure is usually orders of magnitude lower than the levels of exposure in occupational settings giving rise to lung disease. We have been studying the human lung burden of retained inorganic particulates for many years (Abraham and Burnett, 1983) and have developed an ever-expanding database (Abraham et al., 1991) of information on the lung burden in currently over 700 analyses of over 600 lungs. The database contains mostly data from persons with known or suspected aerosol particulate exposures of one kind or another; it also contains data from histologically normal lungs and lungs from persons with lung disease but not known occupational or environmental exposures. Previous studies have examined the relationship of concentrations of a few specific particles to pathologic reactions in patients with specific exposures and/or diseases, such as: sandblasters with silicosis; beryllium ceramics workers with and without chronic beryllium disease; cemented tungsten carbide workers with the unusual pathologic reaction; GIP (giant cell interstitial pneumonia); granulomatous and fibrotic lung disease in persons exposed to metals such as titanium, zirconium or aluminium; and welders. In addition, with the ongoing interest in the relationship of fine particulate aerosols in air pollution to health effects several studies have investigated the potential toxicity of various metals, especially the transition metals, Fe, Ni, V, Cu, Mn and Zn in materials such as residual oil fly ash (ROFA). The higher prevalence of such metals as V in ROFA than in particulates identified in, or recovered from lungs, is consistent with the importance of soluble metals from such particulates. Factors such as particle diameter, surface area, roughness and the presence of surface species are also likely to play critical roles. Metal particulate exposures are also of increasing interest in the etiology and pathogenesis of interstitial lung disease which might otherwise be termed idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis (Kennedy and Chan-Yeung, 1996). Several years ago evidence of metal particulate exposure was

Development, use, and availability of a job exposure matrix based on national occupational hazard survey data

A job exposure matrix has been developed based on potential exposure data collected during the 1972-1974 National Occupational Hazard Survey (NOHS). The survey sample was representative of all U.S. non-agricultural businesses covered under the Occupational Safety and Health Act of 1970 and employing eight or more employees. Potential worker exposure to all chemical, physical, or biological agents was recorded during the field survey if certain minimum guidelines for exposure were met. The job exposure matrix (JEM) itself is a computerized database that assists the user in determining potential chemical or physical exposures in occupational settings. We describe the structure and possible uses of the job exposure matrix. In one example, potential occupational exposures to elemental lead were grouped by industry and occupation. In a second example, the matrix was used to determine exposure classifications in a hypothetical case-control study. Present availability as well as future enhancements of the job exposure matrix are described.

Occupational exposure standards for pharmaceutical agents.

Compared to the wide range of occupational exposure standards available in different countries for industrial chemicals, there are only a few similar standards set for pharmaceutical agents. These substances produce physiological effects in relatively small doses, and there are documented ill-effects from worker exposures, hence the need for such standards. There are different approaches to setting occupational exposure standards for pharmaceutical agents. One derived from the nuisance dust standard may be used, although that may not be wholly appropriate. An approach has been previously suggested for ethinyl estradiol, and this requires the minimal effective dose, a safety factor, an assumption of equal absorption by inhalation as by the oral route, and the volume of air inhaled over an 8-hour day. Toxicological and pharmacological information for zeranol, an animal growth promoter with estrogenic properties, is used with these criteria to obtain an airborne standard. It can be shown that depending on what assumptions are made, there can be more than a tenfold difference in standards reached. There are other difficulties with setting standards for pharmaceutical agents, depending on the group of substances involved. Airborne standards are useful for medicines that are inhaled. A "skin" notation may be needed for those that can be absorbed via the dermal route. Biological standards should also be considered. Provision of standards for pharmaceutical agents will go some way towards protecting exposed pharmaceutical workers.

Oculodermatological findings in workers with occupational exposure to polychlorinated biphenyls (PCBs).

Oculodermatological findings, such as hypersecretion of the Meibomian glands, swelling of the upper eyelids and hyperpigmentation of the conjunctivae are considered typical of "PCB poisoning." They were common clinical manifestations of yusho and yu-cheng, two epidemics in Japan and Taiwan caused by the ingestion of rice cooking oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans. To investigate the prevalence of such abnormalities in a population with long term occupational exposure to PCBs, a group of 326 workers employed in two capacitor manufacturing facilities were investigated in 1976, and 195 of these again in 1979. The median blood values of lower homologues of PCBs were 63 ppb (in plasma) in 1976 and 49 ppb (in serum) in 1979, and of the higher homologues 18 ppb and 17 X 5 ppb respectively. The prevalence of oculodermatological findings potentially related to the effects of PCBs were 9 X 4% and 13 X 3% at the two examinations. There was no significant association between such abnormalities and blood plasma/serum concentrations of PCBs. The observations in this work population exposed to PCBs differ from the yusho and yu-cheng experiences in that fewer clinical abnormalities were found. Suggestions are made that it may be inappropriate to extrapolate findings from the well known PCB poisoning episodes to exposures in occupational settings and that attention should be paid to the importance of polychlorinated dibenzofurans as an aetiological factor in human PCB poisoning.