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The Control of Substances Hazardous to Health Regulations 1994 (COSHH), provide the main British legislation to protect against health risks arising from hazardous substances used at work. Under the regulations, employers have a duty to carry out a suitable and sufficient risk assessment and take steps to ensure exposure is adequately controlled. The paper by Topping et al. (1998) concluded that small firms need more basic, readily available advice on how to effectively control hazardous substances. To meet this need the Health and Safety Executive (HSE) and the Advisory Committee on Toxic Substances (ACTS) have developed a new scheme for the UK. It involves a simple system of generic risk assessments to identify appropriate control strategies and a series of control guidance sheets providing good-practice examples of those strategies for common operations. The approach builds on earlier industry risk banding schemes and HSE's general approach to risk assessment and risk management. To help ensure the advice reaches small firms, HSE is seeking to involve key intermediaries in its dissemination. This paper describes the rationale for the new UK scheme, how it sits in the legal framework, and proposals for its dissemination. The papers by Brooke (1998) and Maidment (1998) set out in detail the technical basis for the scheme.

Market research was carried out to determine industry's perception of occupational exposure limits (OELs) and the extent to which they influence the selection of measures to control exposure. Telephone interviews were carried out with 1000 randomly selected users of chemicals, 400 from establishments with some use of chemicals and 600 from establishments with chemicals in daily use. 150 interviews were also carried out with Trade Union Health and Safety Representatives. The interviews covered basic information on chemicals used, sources of information, risk reduction measures used and understanding of COSHH and OELs. Most respondents came from firms with 10 employees or less (75%, all user group; 57%, heavy user group), closely reflecting the profile of British industry. In contrast, most (77%) Trade Union Health and Safety Representatives came from firms with at least 100 employees. Respondents in the all user group were drawn from across the whole range of industrial activity, whereas the heavy users were concentrated in manufacturing. The results showed that in making decisions on what control measures to use most users rely heavily on information from suppliers and personal experience and rather less on information from sources such as Trade Associations and HSE. Most respondents reported that steps were taken to protect employees. The use of personal protective equipment featured highly, followed by process controls. Little consideration was given to the possibility of substitution. Awareness of COSHH was limited with 65% of the all user group and 53% of the heavy user group being unaware of any legal requirements for establishments which manufacture or work with chemicals. Awareness of OELs was similarly limited with 19% of the all user group and 32% of the heavy user group having any real understanding. The results from Trade Union Representatives showed that overall they are somewhat better informed than chemical users in the small firms surveyed.

This study investigated the environmental conditions on pig farms and the respiratory health of pig farmers and their immunological response to airborne contaminants. Airborne concentrations of dust and ammonia were measured in 20 pig houses; viable microorganisms, endotoxins, and aeroallergens were measured in 6 of these houses, chosen to represent the range in dustiness. The 29 farmers employed on the farms completed a questionnaire and underwent lung function tests; 24 of them provided blood samples for the measurement of specific IgE and IgG antibody to extracts of pig squames and urine, feed components, and bacterial isolates. Mean airborne dust and ammonia concentrations in the pig houses ranged from 1.66 to 21.04 mg/m3 and from 1.50 to 13.23 ppm, respectively. Factors affecting these concentrations include time of year, feed systems used, and levels of ventilation. There was no direct relationship between airborne dust and ammonia concentrations. Airborne microorganisms ranged from 10(5) to more than 10(7) colony-forming units (cfu)/m3; most were bacteria, with few fungi or thermophilic actinomycetes isolated. Gram-positive bacterial genera (Staphylococcus, Micrococcus, and Bacillus spp.) predominated. Concentrations of endotoxin in collected airborne dust were low. Work-related respiratory symptoms, typically chest tightness/wheeze and nasal and eye irritation, were reported by 23 of the 29 workers. Three farmers had specific IgE to pig squames or urine and eight to feed components but none to the microbial extracts. Specific IgG to pig squames or urine and to feed components was demonstrated in 14 and 9 workers, respectively. Specific IgE responses occurred mainly in subjects with chest tightness or wheeze, although specific IgG responses were not related to symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of pyroglyphid mites in house dust allergy is well established and the major allergens from the common house dust mites (Dermatophagoides species) have been characterized. There is, however, relatively little progress in the understanding of the human IgE response to non-pyroglyphid storage mites, allergenic crossreactivity with other mite species and extent of environmental exposure. We studied 196 individuals from an urban environment who were not occupationally exposed to storage mites and found a 24% prevalence of specific IgE antibody to Dermatophagoides pteronyssinus and a 14% prevalence of RAST positivity to at least one of three storage mites, Acarus siro, Lepidoglyphus destructor and Tyrophagus longior. All individuals with a positive RAST to storage mites had specific IgE to D. pteronyssinus. RAST inhibition studies with the eight sera with greater than 2% RAST binding to both families of mites showed considerable crossreactivity between D. pteronyssinus and the storage mites A. siro and T. longior and limited crossreactivity between D. pteronyssinus and L. destructor. This suggests that at least some of the response to storage mites observed by direct RAST is a consequence of crossreactivity with the more abundant D. pteronyssinus.

This study describes sensitization to a diazonium salt intermediate, diazonium tetrafluoroborate (DTFB), produced during the manufacture of a fluorine polymer precursor. Most of the workers exposed to DTFB powder complained of respiratory and mucosal irritation. However, some of these individuals had symptoms typical of occupational asthma. Clinical and immunologic studies, including bronchial provocation testing and specific IgE measurements, were performed on two individuals with asthmatic symptoms associated with exposure to DTFB. These studies confirmed a diagnosis of occupational asthma. In an investigation of 43 other exposed workers in two separate factories handling the diazonium compound, specific IgE antibodies to DTFB-human serum albumin conjugate were found in 20% of individuals. There was a good correlation between specific IgE and exposure-related respiratory symptoms, which suggests an IgE-mediated pathogenesis. DTFB-human serum albumin conjugates were characterized by electrophoretic techniques, and it was found that conjugates prepared at pH 10 elicited optimum IgE binding in RAST. In vitro cross-linking of albumin by DTFB was demonstrated but had no effect on RAST binding. Our findings on the effect of pH and polymerization on IgE binding support proposed mechanisms for in vivo conjugation and provide information on the antigenic determinants important in IgE recognition of hapten-carrier protein conjugates.

We describe seven women with asthma induced by occupational exposure to an acid anhydride, tetrachlorophthalic anhydride (TCPA), an epoxy resin hardening agent. Inhalation tests with TCPA at atmospheric concentrations of less than one tenth of a manufacturer's recommended exposure limit provoked asthmatic reactions in the four women tested. None had evidence of pretest bronchial hyperreactivity. Immediate skin prick test reactions were elicited in the seven subjects by a conjugate of TCPA with human serum albumin (TCPA-HSA) but not in others tested. Specific IgE antibody levels to TCPA-HSA, measured by radioallergosorbent test scores, were significantly elevated in the seven, but not in TCPA-exposed and unexposed comparison groups. These results imply that occupational asthma caused by TCPA is an allergic reaction mediated by specific IgE antibody.

Storage mites (acarid mites) are related to the house dust mite but are usually found in agricultural environments. They have been shown to cause allergic symptoms in Scottish farmworkers exposed to stored hay, but whether farmworkers who grow and store grain are also at risk is unknown. One hundred and one farmworkers on 22 Essex farms with grain storage facilities (88% of the available workforce) participated in a survey of respiratory symptoms, with skin tests and determination of serum levels of IgE specific for mite species, including storage mites. Of the 101 workers, 21 reported attacks of cough, wheeze, or breathlessness after exposure to stored grain and 15 reported nasal symptoms after grain exposure. Storage mite specific IgE was found in 59% of farmworkers with work related respiratory symptoms, in 60% with work related nasal symptoms, and in only 9% of symptomless farmworkers. Work related respiratory and nasal symptoms were also significantly associated with atopy, and with positive skin test responses and serum IgE specific for Dermatophagoides pteronyssinus. Storage mites were found in grain samples from 16 farms in which grain was sampled, whereas D pteronyssinus was not found in any. The close association between serum storage mite specific IgE and occupational respiratory symptoms suggests that storage mites may be responsible for respiratory symptoms in these Essex farmworkers exposed to grain.

A questionnaire survey of over 400 workers handling reactive dyes showed that over 15% had work related respiratory or nasal symptoms. Forty nine employees with symptoms were referred to chest clinics for detailed assessment. It was considered that in 19 the symptoms could be attributed to an irritant response to a variety of chemicals, including hydrochloric acid vapour, sulphur dioxide, and reactive dyes. Symptoms in 24 were attributed to an allergic reaction to a specific agent; in most (21) to one or more reactive dyes. Two patterns of allergic lower respiratory symptoms were identified; an immediate response of short duration and a longer lasting response, usually of several hours, sometimes accompanied by nocturnal asthma. A radioallergosorbent test (RAST) screen containing the most commonly used reactive dyes was used to detect specific IgE. Allergic symptoms to reactive dyes were strongly associated with specific IgE (17/21 employees) and atopy (18/21). Irritant symptoms were also associated with atopy (13/19) but only weakly associated with specific IgE (7/19).

Hypersensitivity to reactive dye powders has been recognised for a number of years, although the extent of sensitisation amongst dye house operatives and the immunochemistry of the dye molecules has not been investigated. We have developed a radioallergosorbent test (RAST) to detect specific IgE to reactive dye-human serum albumin (HSA) conjugates. From a total of 19 dye-HSA conjugates, positive RASTs were found in six workers with allergic symptoms associated with dye exposure, while six asymptomatic case-matched controls were negative. Sera with raised total IgE (up to 4300 kU/l) from unexposed workers gave negative results except for two conjugates which gave a weak positive at 4300 kU/l and one which gave weak positives at all concentrations tested (750-4300 kU/l). RAST demonstrated that the antibody was specific for the complete dye-HSA conjugate. Substitution of bovine serum albumin (BSA) for HSA in the conjugate markedly reduced immunoreactivity and free hapten gave lower inhibition than the complete conjugate. Comparison of the dye-HSA RAST with a RAST using dyed discs showed that the latter did not correlate well with symptoms and was influenced by the total IgE concentration.

We have explored the antigenic and allergenic relationship between the house dust mite Dermatophagoides pteronyssinus and three species of storage mite, Glycyphagus destructor, Acarus siro, and Tyrophagus longior. Crossed immunoelectrophoresis demonstrated that all the mite extracts contained multiple antigens but that there was only limited cross-reactivity between the different species. Six sera were obtained from workers exposed to storage mites and with occupationally related lower respiratory tract symptoms. All workers had specific IgE to D. pteronyssinus and to one or more of the storage mites. The pattern of reactivity varied between the different sera, two responded primarily to D. pteronyssinus and A. siro and four sera to D. pteronyssinus and G. destructor. Only weak responses were observed to T. longior. RAST-inhibition and affinity-absorption experiments demonstrated that D. pteronyssinus had at least three groups of distinct allergenic determinants, determinants specific to D. pteronyssinus, determinants shared with A. siro, and determinants shared with G. destructor. Similarly, both A. siro and G. destructor have specific allergenic determinants and determinants shared with D. pteronyssinus. The findings demonstrate the complexity of the immunologic responses to the different mite species.

We describe occupational allergy to castor bean in workers in a felt manufacturing plant. Twenty-six (37%) of the workers complained they were affected by the felt and were examined by us. Of these, 12 were considered to have occupational allergy. These 12 subjects had raised specific IgE levels to both felt and castor bean extracts. In addition, three subjects without occupational allergy had raised specific IgE. The presence of castor bean allergens in the felt was suggested by the correlation between the RAST scores to the felt and castor bean and confirmed by RAST inhibition experiments. The RAST results correlated well with the results of skin prick tests to felt and castor bean extracts. In addition it was found that atopy did not predispose the workers to castor bean allergy.

Patients with work-related respiratory symptoms caused by inhaled acid anhydrides (trimellitic (TMA), phthalic (PA), tetrachlorophthalic (TCPA), and maleic anhydrides) have specific IgE antibody. The antibody is specific for a conjugate of the sensitizing anhydride (the hapten) and human serum albumin (HSA). We have investigated the specificity of the reaction to determine whether the antibody is directed against (1) the anhydride, (2) new antigenic determinants formed by conjugation of albumin with the anhydride, or (3) the complete anhydride-HSA conjugate. For the patients sensitized to TCPA and TMA, RAST inhibition studies demonstrate the anhydride-HSA conjugate to be a more effective inhibitor of RAST than the sodium salt of the anhydride or an anhydride-bovine serum albumin conjugate, whereas for those sensitized to PA, the free hapten is almost as an effective inhibitor as the conjugate. With each sera HSA conjugates of anhydrides to which the patient is not sensitized are weaker inhibitors than the sensitizing anhydride-albumin conjugate. These results provide strong evidence that for the patients sensitized to TCPA and TMA, the antibody combines with the anhydride and the spatially adjacent portion of the HSA molecule, whereas in the patients sensitized to PA, the antibody is specific for the hapten.

The workforce at a biotechnology plant producing citric acid by fermentation of molasses with a strain of Aspergillus niger was studied. A combination of a respiratory questionnaire and clinical assessment identified 18 subjects (4.9% of the workforce) with work related bronchospasm. In nine of these evidence of sensitisation to A niger was obtained by skin prick tests and radioallergosorbent test (RAST) using as an antigen an extract of the A niger culture fluid from the process. Of the 325 subjects without work related bronchospasm, only nine (2.7%) had a positive prick test. There were no subjects with symptoms of extrinsic allergic alveolitis. Investigation into the source of the antigen showed that whereas, in some areas of the plant, A niger spores were present, in others there were no detectable spores. In these areas, however, extracts of filters from air samplers were shown by RAST inhibition to contain A niger antigens, indicating that the culture fluid was generating airborne antigen. RAST inhibition studies showed that the A niger culture fluid used in the process contained antigens that were not present in a commercially available A niger extract, thus emphasising the importance in this type of investigation of using antigens prepared from material to which the workers are exposed.

The technique of isoelectric focussing in polyacrylamide gel has been developed to a preparative mode. Using the improved technique cocksfoot (Dactylis glomerata) pollen has been split into many components, and the allergenic reactions of the preparations have been studied by passive transfer in animal skin and by RAST.

The two present systems of units for the strength of allergen extracts, Noon and p.n.u. are both unsatisfactory. A new activity unit, based on skin prick in humans, is described, and its relationship to in vitro tests is explored. Potency limits for provocation materials used for skin prick tests are suggested.

Respiratory symptoms among six employees in wool dye-houses in the United Kingdom were investigated. Clinical histories revealed that all had work-related respiratory symptoms, which they associated with exposure to Lanasol dyes. Five of the six subjects had specific Immunoglobin E to human serum albumin conjugates of one or more of the dyes to which they were exposed, providing evidence of sensitization to these dyes. In two subjects there was a definite association between symptoms to a particular dye, and specific IgE to an albumin conjugate of that dye. Specific IgG was found in exposed subjects, irrespective of the presence of allergic symptoms, indicating that specific IgG reflects exposure rather than clinical sensitization. Four of the six subjects had specific IgG4; this was only present in the subjects with respiratory allergy and specific IgE.

A number of workers packing ipecacuanha tablets were complaining of allergic symptoms. Skin-prick tests, RAST and an assessment of clinical history by interview were used to confirm the presence of work-related allergy. Specific IgE antibodies to ipecacuanha were detected and the occurrence of antibodies correlated with the incidence of allergic symptoms. The individuals with positive RAST scores had been employed, on average, longer than those with negative scores. It was found that atopy did not predispose the workers to work-related allergy and that there was no correlation between smoking and respiratory symptoms in this population.

A survey was carried out of a population of workers exposed to tetrachlorophthalic anhydride, an acid anhydride epoxy resin curing agent known to cause asthma. Using a radioallergosorbent test with a tetrachlorophthalic anhydride human serum albumin conjugate, specific IgE antibody was detected in serum from 24 out of 300 factory floor workers exposed to tetrachlorophthalic anhydride. Of these 24, 20 (83.3%) were current smokers compared with 133 (48.2%) of 276 without antibody (p less than 0.01), and there was a weaker association with atopy, defined by skin tests with common allergens. Smoking and atopy interacted, the prevalence of antibody being 16.1% in atopic smokers, 11.7% in non-atopic smokers, 8.3% in atopic non-smokers, and nil in non-atopic non-smokers (p less than 0.025). Smoking may predispose to, and interact with atopy in, the production of specific IgE antibody to this hapten protein conjugate.

In this study, undertaken to identify the cause of allergy in several upholstery workers in a furniture factory, the workers were handling several different materials, including glue, silicone spray, upholstery fabrics, and felt. Radio-allergo-sorbent test (RAST) assays showed that sera from sensitised workers contained specific IgE towards the felt; however, further investigations using RAST showed that the allergen was not the felt itself but a contaminant of the felt. The felt was manufactured from sacks, some of which had been used to store castor beans. The sera with raised IgE to the felt also had raised IgE to the castor bean extract. By means of RAST inhibition we confirmed that castor bean allergens in the felt were solely responsible for the raised IgE in the sera. The in-vitro RAST results were found to correlate well with the in-vivo pick tests and clinical symptoms.

One hundred thirty-three grain-store workers employed at a regional grain store in Essex, U.K., participated in a survey of respiratory symptoms, lung function, bronchial responsiveness to methacholine and skin tests, and specific IgE to occupational allergens, including extracts of five storage-mite (SM) species and grain extracts. Previously reported associations between occupational respiratory symptoms and cigarette smoking, and symptoms of bronchial hyperresponsiveness to methacholine were confirmed. This study also disclosed significant associations between work-related symptoms (WRS) and positive skin tests and/or specific IgE to SMs, but not between WRSs and positive skin tests or specific IgE to Dermatophagoides pteronyssinus, or between WRSs and positive skin tests to grain. These findings suggest that in United Kingdom grain workers, allergic responses to SMs may be another factor responsible for WRSs in grain-store workers.

The possible role of human dander in house dust allergy was investigated. Naturally shed human mite-free skin squames were collected from bedding and used to prepare a human dander extract. When the extract was coupled to cyanogen bromide-activated paper discs, and used in the RAST assay, IgE titres to the skin extract were observed in the sera from several patients with house dust allergy. The sera with IgE to the skin extract also had high IgE titres to either house dust, D. pteronyssinus or cat fur. RAST inhibition studies revealed cross-reaction between the human skin extract and both a D. pteronyssinus extract and a cat fur extract.

The cadmium body burden, blood and urine cadmium concentrations, and renal function were studied in a group of 53 cadmium solderers. The results showed raised blood and urine cadmium concentrations and raised cadmium body burden in all workers (31) with more than five years exposure, with 27 having urine cadmium concentrations in excess of the proposed biological threshold of 10 nmol/mmol creatinine. Renal tubular dysfunction was found in 17 of the subjects with more than five years exposure and in one this was associated with glomerular dysfunction. These data indicate that cadmium body burden and frequency of tubular dysfunction in end users of cadmium may be as high as those found in smelters or production workers. Subjects with tubular dysfunction did not show greatly increased urine cadmium concentrations compared with those without dysfunction, supporting a previous suggestion that tubular dysfunction occurs before the wash out of cadmium from the kidney. At the time of our study, cadmium exposure stopped as cadmium free soldering rods were introduced. Repeat urine samples from 19 subjects, one to two years after exposure ended indicated that there was no further increase in the level of excretion of low molecular weight proteins, perhaps indicating that the tubular proteinuria does not increase or more severe renal dysfunction develop without continuous exposure.

With the combined use of skin tests, RAST and isoelectric focusing, a potency profile of a cocksfoot ((Dactylis glomerata) pollen extract was prepared. It was found that two fractions with pI 4.5 and 6.0 were the most allergenic, had the highest protein concentration and were also the most easily extracted. The importance of converting mean weal sizes into potency units when comparing the allergenicity of pollen fractions is emphasized.

An enzyme-linked immunosorbent assay (ELISA) for urinary retinol-binding protein (RBP) has been developed and compared with urinary beta 2-microglobulin for the detection of tubular proteinuria. The assay has a working range of 10 to 250 micrograms of RBP per liter of urine. The within-assay CV was 3.2-7.1%, the between-assay CV 12.5%. A control population of 118 male subjects gave a geometric mean urinary RBP concentration of 7.7 micrograms per millimole of creatinine and a 95th centile of 22 micrograms per millimole of creatinine. Comparison of urinary RBP and beta 2-microglobulin concentrations in 80 control subjects and 117 subjects exposed to cadmium fumes gave correlations of r = 0.59 and 0.91, respectively. Of the 117 subjects exposed to cadmium fumes, 103 gave both RBP and beta 2-microglobulin concentrations on the same side of the upper 95th centile values of 22 and 38 micrograms per millimole of creatinine for RBP and beta 2-microglobulin respectively (Chi-square analysis p less than 0.001), demonstrating that RBP and beta 2-microglobulin detect tubular proteinuria with equal sensitivity and specificity. ELISA and an established latex immunoassay gave well-correlated results.

Seven patients with occupational asthma caused by a chemical, tetrachlorophthalic anhydride (TCPA), left their work in 1980. They have subsequently avoided TCPA exposure and have been followed until 1985. One patient died in 1981. The six living patients reported continuing symptoms suggestive of asthma, and five who were studied in 1985 demonstrated mild bronchial hyperresponsiveness (histamine concentration provoking a 20% fall in FEV1 range 2.7 to 12.5 mg/ml). Specific IgE antibody to TCPA conjugated with human serum albumin was measured by a radioallergosorbent test and detected in all patients. After avoidance of exposure, specific IgE fell exponentially with a half-life of 1 year. Specific IgE was still detectable in 1985, and throughout the follow-up period, prick tests with the conjugate elicited immediate skin responses. In 1981 four patients had inhalation tests with TCPA, and specific IgE rose afterward and then fell again.

Previous studies have shown that allergy to storage mites is a significant contributor to allergic disease among an isolated farming community in the Orkneys. The present study was undertaken to determine the prevalence of disease due to storage mites among farmers on the mainland of Scotland. Of the 290 subjects employed on 102 randomly selected farms studied, eighty-seven (30%) reported allergic symptoms on entering barns or byres, and prick tests to storage mites were positive in 62 (21%). Rhinitis and conjunctivitis together were the more frequently reported symptoms, with less than half the subjects recording respitatory symptoms. Specific IgE antibody to storage mites was detected in 43% of subjects reporting allergic symptoms associated with hay dust. Specific IgE to storage mites was strongly associated with atopy in those subjects who reported allergic symptoms.

A cocksfoot (Dactylis glomerata) pollen extract has been fractionated by isoelectric focusing in polyacrylamide gel, the separated components extracted from the gel and assayed by three methods: prick tests in human skin, RAST and PCA tests in monkey skin. Prick testing in human skin showed that subjects responded differently to the separated components, indicating the presence of more than one antigenic determinant, and a profile of antibody activity against each fraction could be constructed. In general, good agreement was observed between RAST profiles and skin test profiles, although some patients who gave positive skin tests lacked circulating IgE and consequently did not give a RAST profile or a monkey PCA. These studies emphasize the current difficulty in attempting to isolate a single pure allergen from cocksfoot which can be used either diagnostically for the detection of pollen allergy, or for the standardization of diagnostic extracts.

A description is given of a hygiene investigation made to determine workers' exposure to airborne microorganisms and antigen in the slicing area of a sugar beet refinery following complaints by the workers of work-related respiratory symptoms. Dust concentrations in the slicing area were not high (up to 3.5 mg/m3), but there were many airborne microorganisms (200,000 colony forming units/m3), mostly gram-positive bacteria. Of 15 workers, 7 had precipitins to a sugar beet extract. Of these 7, there were 5 who also had precipitins to an extract of dust collected on a 'Staplex' filter. There was a line of identity between the beet and dust extracts, indicating the dust contained appreciable quantities of beet antigen. As a result of these findings, local exhaust ventilation was installed before the next slicing season. Further investigations were made near the beginning and end of this second season. The results showed lower dust concentrations and markedly fewer numbers of airborne bacteria. Although total numbers of bacteria fell, numbers of gram-negative bacteria increased and, at the end of the season, comprised 20% of the total bacterial numbers. Specific immunoglobulin G (IgG) concentration in the workers' serums fell between the two slicing seasons and then remained constant through the next slicing season. This reflected the environmental measurements that showed lower dust concentrations after the installation of exhaust ventilation equipment.

Biochemical indicators of renal dysfunction have been compared with liver and kidney cadmium levels measured by neutron activation analysis in a group of 37 cadmium smelters. Higher than normal concentrations of cadmium in the liver reflect past exposure; they were associated with evidence of renal dysfunction in workers exposed to cadmium for more than 10 years. A small group of 6 workers exposed to cadmium for only a short time (mean = 4.6 years) had high hepatic cadmium concentrations but normal renal function. Longitudinal studies are required to establish the natural history of renal dysfunction following cadmium accumulation in industrial workers.