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The pathophysiological mechanisms of organic diisocyanate-induced respiratory disease remain largely unknown. Some 20% of patients have specific antibodies towards diisocyanate monomers whereas even in this circumstance their presence does not correlate very well with results in clinical provocation tests. The formation of diisocyanate haptens is the trigger for the immunological reactions. However, it is known that the reactions with protein and other macromolecules may be slow and hydrolysis of the isocyanate moities to corresponding amines as catalyzed by bicarbonate is more rapid. The liberated amines, or their intermediates, probably have an important role in the activation of tissue thromboplastin activator, loss of serum antitrypsin activity, and, finally, in neurogenic inflammation. Hypothetically, susceptible individuals probably include those which are slow acetylators of exogenous amines and carries of heterozygous antitrypsin phenotypes.

The case of a man exposed during 25 years to vibration while maneuvering a heavy earth moving tractor is reported. The first clinical manifestation of hand-arm vibration syndrome was a bilateral Raynaud's phenomenon followed five years later by digital necrosis. The arteriography revealed a proximal and bilateral ulnar artery occlusion. Bilateral median nerve conduction abnormalities were also present. Vibration exposure level was much higher than the threshold level proposed by the European Commission. Laboratory examinations for vasculitis and other vascular diseases were all negative. The purpose of this report is to show that vibration can be responsible for proximal occlusion of a medium sized artery and severe neurovascular abnormalities which must be distinguished from the usual vasospastic Raynaud's phenomenon and the classical hypothenar hammer syndrome. An early and correct diagnosis is crucial because continued repetitive trauma can result in irreversible ischemic injury and loss of digits.

Field surveys of diisocyanates at the workplaces in Switzerland and particularly in car repair shops, where HDI was the most used, showed that the monomer levels comply with the Swiss permissible exposure limit (PEL) in the great number of situations. Cases of medical surveillance associated with industrial hygiene measurements demonstrate that occupational asthma was also observed in situations where the monomer concentrations are low although high peaks of prepolymers are often recorded. From the statistical data on compensations, the annual incidence of occupational asthma over the period 1988 to 1992 remains around 54 cases with a mean cost of 21,000 sFr. per case per year. It is suggested that a PEL on the prepolymers should be introduced in the Swiss PEL list to enhance the efficiency of prevention policy.

Thirty serum samples from clinical cases of flour hypersensitivity were analyzed for wheat or rye flour protein antibodies. The patients included 20 bakers and 10 others who also had occupational flour exposure. Twenty-three cases had antiflour antibodies which recognized antigens other than control sera in the flour protein patterns. The immunologic response of individual cases seemed very variable in view of the numerous differences between the cases in the antigen-antibody reactions. For the practical purposes, the flour protein antigens were divided in three groups, i.e., those larger than 80 kDa, those between 80 and 50 kDa and those smaller than 50 kDa. Cases with flour-induced dermatitis (n = 8) showed sensitization towards antigens in all size classes while those with rhinitis or asthma showed more antigens with a molecular weight less than 50 kDa. The test offers a possibility to independently verify an exposure to flour while it does not substitute for the conventional immunologic diagnostic tests.

Cadmium is widely used in industry, causing exposure of workers and environmental pollution because of its persistence in the biosystems. Its very long half-life in the human organism causes its accumulation over the lifetime in liver and kidneys. Cadmium ions have a high affinity for tissue thiols, induce the synthesis of a carrier cysteine-rich polypeptide called metallothionein, and impair proteoglycan metabolism. Significant renal effects include tubular nephropathy manifested by proteinuria, amino aciduria, glucosuria, phosphaturia, and calcium wastage. Chronic sequels include decrease in the glomerular filtration rate and increased risk of kidney stone disease. Biological monitoring of cadmium absorption includes determination of urinary cadmium and of low molecular weight marker proteins, such as beta2-microglobulin or retinol binding protein, the tubular reabsorption of which is impaired before a frank proteinuria.

Six foundrymen occupationally exposed to cadmium fumes excreted in random urine samples 4.8 +/- 2.9 micrograms cadmium/g creatinine (+/- S.D.). Six controls excreted 0.15 +/- 0.09 microgram/g creatinine (+/- S.D.). The excretion of glycosaminoglycans by exposed men (2.3 +/- 1.1 mg/mmol creatinine, +/- S.D.) did not differ from that of controls (2.3 +/- 1.6 mg/mmol, +/- S.D.). However, electrophoretic analysis of the isolated urinary proteoglycan fraction revealed a dose-dependent progressive increase in the intensity of two bands with a molecular weight between 45,000 and 50,000. In control urines and in samples with urinary cadmium less than 3 micrograms/g creatinine, only one major band with a molecular weight of 100,000 was detected. The changes may serve as early indicators of the harmful effects of cadmium on the proteoglycan-containing barriers of the nephron.

The excretion of urinary glycosaminoglycans by five occupationally exposed men with urinary cadmium levels of 1 to 6.5 micrograms/g creatinine did not differ significantly from that of six age-matched non-exposed controls (2.8 +/- 1.8 mg/mmol creatinine vs. 2.3 +/- 1.6 mg/mmol creatinine, +/- S.D.) as analyzed in random urine samples. However, there was a cadmium concentration-dependent increase in the excretion of 50 kD proteoglycan as analyzed by polyacrylamide electrophoresis of the isolated proteoglycan fraction in the same urine samples. This may represent the early dose-dependent effect of cadmium on renal tubules which leads to decrease in the renal cell sialic acid content and protein excretion at higher exposure levels.

Eleven subjects with clinical bronchial hyperreactivity towards hexamethylene diisocyanate used in their work and verified by spirometry before and after a shift were screened for their antitrypsin phenotypes by isoelectric focusing. One third were M1M1 homozygotes (over 50% in controls) while the rest were heterozygotes comprising one case, each, of M1S and M1I (expected frequencies 5 and 0.5%, respectively). It seems that heterozygous alpha 1-antitrypsin carriers may be at a greater risk to develop a pulmonary disease in the organic diisocyanate exposure than the homozygotes.

Nine sawmill workers were divided into two groups according to their exposure to 2-ethylhexanoic acid, (EHA), a pesticide which has replaced the older pentochlorophenol. The men with lower exposure excreted 30 +/- 10 nmol EHA/mmol creatinine (mean +/- SD, n = 4) in urine samples taken after the workshift, whereas men with higher exposure excreted 1.8 +/- 1.6 mumol EHA/mmol creatinine (mean +/- SD, n = 5, p less than 0.01). The urinary ornithine and arginine concentrations were at the lower exposure 1.4 +/- 0.4 and 1.5 +/- 0.8 mumol/mmol creatinine, respectively (mean +/- SD, n = 4), and they increased significantly (p less than 0.01) to 4.5 +/- 2.5 and 3.2 +/- 1.5 mumol/mmol (mean +/- SD, n = 5), respectively, at the higher exposure. This might have been caused by the inhibitory effect of EHA on urea synthesis which was partially compensated for by elevated arginine and ornithine concentrations to drive the urea cycle more efficiently.

Twelve workers (nine men and three women with a mean age of 39.5 +/- 8.9 years) with occupational exposure to trinitrotoluene had a mean duration of exposure of 6.8 +/- 4.7 years. The general physical findings were minimal, but ophthalmologic examinations showed bilateral peripheral cataracts in six of the 12 workers. Cataracts were visible only with maximal mydriasis and were continuous or annular opacities at the equator. The cataracts did not interfere with visual acuity or visual fields. Only one worker with and one without cataracts had increased serum alanine aminotransferase and bilirubin levels, possibly associated with trinitrotoluene exposure.

Decreased erythrocyte glutathione s-transferase activity was found in workers exposed to hot rubber fumes in two-roll mill and calender departments (6.6 +/- 0.9 and 6.8 +/- 0.8 mumol/min X mg haemoglobin, respectively vs 8.4 +/- 0.5 in controls). This trend was also noted in the general category of all rubber exposed workers without stratification according to their task (7.6 +/- 0.5, n = 30). This result was contrary to that expected, as the cases with the lowest values had the greatest urinary thioether excretion. The thioethers are the end-products of the enzyme-catalyzed glutathione conjugation reaction aimed at the inactivation of potentially toxic chemicals. Thus, it appears that the assay of erythrocyte glutathione s-transferase activity is not very informative about exposure, although the enzyme assay might disclose other, so far unknown, biological effects of reactive rubber chemicals.

An hygienic survey for hydrogen sulfide, methyl mercaptan and its derivatives and sulfur dioxide in kraft mills and in sulfite mills revealed concentrations varying from 0 to 20 ppm hydrogen sulfide, 0 to 15 ppm methyl mercaptan and comparable amounts of dimethyl sulfide with dimethyl disulfide up to 1.5 ppm. The greatest emissions were detected at chip chutes and evaporation vacuum pumps. Batch operations yielded clearly higher sulfur dioxide concentrations (up to 20 ppm) as compared to a continuous ammonia-base digester. Furthermore, there was a strong correlation with the season in the sulfite mills where higher concentrations were found in the winter when natural ventilation was poorer. As to the health effects, the exposed workers complained of headaches and a decrease in concentration capacity more often than matched controls. The number of sick leaves was greater in the exposed workers than among the controls.

Exposure of workers to toluene diisocyanate monomer in a factory producing flexible polyurethane was measured using impinger and reagent-impregnated filter sampling. These techniques yielded highly concordant results so that the facile filter techniques can be recommended. The personal exposures were compared with the individual excretion of amine metabolites from the parent toluene diisocyanates. The excretion was linearly related to the product of sampling time and concentration. The biological half-lives of the amines proved to be short so that urine should be sampled 2 h after the exposure. The percutaneous absorption of the monomers could also be controlled.

Objective:To investigate the usefulness of surrogates for individual susceptibility to organic diisocyanates in occupational asthma.Subjects:All new cases declared to the Swiss National Accident Insurance Company (SUVA) for establishment of a case for compensable occupational disease during 1993. Sixty-nine persons, of whom three were women, were suspected of having occupational asthma due to isocyanates. Of these, 47 subjects fulfilled the criteria to be accepted as an occupational disease case.Methods:All subjects were studied clinically and gave a blood sample for the phenotyping of their alpha-antitrypsin status and for immunological studies. The subjects were also given a peroral dose of caffeine for the determination of their N-acetylation capacity. Finally, those with an occupational disease were subjected to the methacholine provocation test.Results:Forty-four persons with occupational disease, out of 47, were heterozygous antitrypsin carriers and/or slow acetylators of primary amines. In the bronchial provocation with methacholine, 12 of these subjects had an unaltered response and seven had a mild reaction, 13 a moderate one and 15 a severe reaction.Interpretation:The study confirms the finding that slow N-acetylators are susceptible to asthma from exposure to common diisocyanate monomers at work. The same applies to heterozygous antitrypsin-phenotype carriers. Thus, the use of these markers may reinforce the diagnostic procedure, but they cannot completely replace the immunological tests. [ABSTRACT FROM AUTHOR]

Objectives: Ethylene glycol ethers and their acetates are widely used in industry, because of their hydrophilic and simultaneously lipophilic properties. Ethylene glycol ethers and their acetates are mainly metabolised to alkoxyacetic acids, but there is also a minor pathway through ethylene glycol to oxalic acid. The main pathway of ethylene glycol ethers is associated with significant clinical or experimental health effects and the minor pathway is also interesting because formation of urinary stones depends principally upon the urinary concentration of oxalate and calcium.Methods: Excretion of alkoxyacetic and oxalic acids was examined among silkscreen printers for an entire working week. The aim of the study was to evaluate alkoxyacetic acids as early indicators of exposure to glycol ethers and to evaluate their toxicity to kidneys. The load of alkoxyacetic and oxalic acids was compared with the excretion of calcium, chloride, ammonia, and glycosaminoglycans (GAG). Morning urine was chosen for the main analysis, as the overall metabolite, ethoxyacetic acid (EAA), has a long elimination time from the body.Results: The excretion of calcium increased according to the urinary alkoxyacetic acid load. The excretion of ammonia and chloride was higher among the exposed workers than among the controls. The highest urinary alkoxyacetic acid load was also associated with increased excretion of GAG, which may reflect the toxicity of metabolites of ethylene glycol ether. The excretion of GAG correlated positively with that of calcium in the printers with highest exposure. The tendency to form urinary stones was 2.4-fold higher among silkscreen printers than among office workers.Conclusion: On the basis of renal effects our study indicates the need for establishing a new biological exposure limit before a workshift that is clearly below 100 mmol ethoxyacetic acids per mol creatinine in morning urine of people occupationally exposed to ethylene glycol ethers. [ABSTRACT FROM AUTHOR]