Vito Foà

The speciation of the chemical forms of arsenic in the biological monitoring of exposure to inorganic arsenic

Total As content may be determined in blood and urine by means of an AAS method that involves reduction of As to its volatile hydride and ashing at 600 degrees C with MgO and Mg (NO3)2. Separation of inorganic As (InAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMAA) by ion-exchange chromatography, followed by direct AAS analysis, allows the determination of each As species in the urine. In a reference population of 148 subjects with only normal environmental exposure to As, total As concentration in the urine averages 17.2 +/- 11.1 micrograms/l. Urinary As consists of 10% each of InAs, MMAA and DMAA, the remaining 70% consisting of other forms of organic As. Blood As concentration averages 5.1 +/- 6.9 micrograms/l and correlates significantly with the urinary concentration of InAs and the sum of its metabolites (InAs + MMAA + DMAA). Inorganic arsenic undergoes methylation in the organism. After ingestion of high quantities of As2O3, the time course of excretion of its metabolites indicates that As methylation occurs by a saturable mechanism. In workers exposed to As2O3, InAs, MMAA and DMAA are the only chemical forms of As excreted in the urine that are relevant to a study of occupational exposure. Blood As concentration is proportional to exposure and correlates only with urinary DMAA excretion; DMAA seems to be the most appropriate single indicator of exposure. At high levels of exposure (total As excretion above 200 micrograms/l), As accumulates in the organism and DMAA excretion reflects its accumulation. At low levels of exposure (total As excretion below 50 micrograms/l) a short-term accumulation does not occur and the best biological indicator of exposure is InAs excretion. Seafood ingestion brings about a marked increase in urinary excretion of total As that lasts for 24-48 h and is not accompanied by any increase in InAs, MMAA or DMAA excretion. Organic As from seafood does not mix with the pool of inorganic As in the organism and may be separately detected in urine. In the biological monitoring of human exposure to As, particularly in the case of high urinary values, the speciation of the chemical forms of As in urine is necessary in order to establish with certainty the source, industrial or alimentary, of exposure.

Effects in man and rabbits of inhalation of cotton dust or extracts and purified endotoxins

Cavagna, G., Foá V., and Vigliani, E. C. (1969).Brit. J. industr. Med.,26, 314-321. Effects in man and rabbits of inhalation of cotton dust or extracts and purified endotoxins. The incidence of byssinosis in workers in a cotton card-room, where the airborne concentration of bacterial endotoxins was 7·2 μg./m.3, was 32%; and 47% in a hemp card-room where the endotoxin concentration was 8·7 μg./m.3; no cases were observed among workers exposed to only traces of endotoxins. The effect of the inhalation by aerosol of purified Escherichia coli endotoxin on F.E.V.1·0 and F.V.C. was studied in normal subjects and in patients with chronic bronchitis. A significant reduction in F.E.V.1·0 lasting more than 6 hours was observed in two out of eight normal subjects, in one out of three subjects with chronic bronchitis inhaling 80 μg. endotoxin, and in one out of four subjects with chronic bronchitis inhaling 40 μg. endotoxin. These results show that the inhalation of bacterial endotoxin can produce, in some individuals, changes in F.E.V.1·0 similar to those experienced on Mondays by some card-room workers. A study of the mechanism of pathogenesis of inhaled bacterial endotoxins was carried out on rabbits subjected for 20 weeks to aerosols of purified E. coli endotoxin (20 μg./day) and cotton extract (2 mg./day). This treatment produced patterns of bronchitis: i.e., a increase in the respiratory tract fluid with increased protein content and characteristic histopathological changes. The bronchitis occurred after the appearance of cross-reacting circulating antibodies against E. coli endotoxin and cotton extract. These antibodies were detected with the haemagglutination tests after the first three weeks of treatment, and in subsequent weeks reached progressively higher titres, up to a maximum of 1:512. A challenging aerosol of 0·1 mg. E. coli endotoxin in two rabbits and 10 mg. cotton extract in another two of the rabbits treated as above produced a marked increase in pulmonary resistance lasting more than two hours. In control rabbits a challenging aerosol of 1 mg. endotoxin or 100 mg. cotton extract caused only a moderate increase in pulmonary resistance, which returned to normal in less than one hour. It may be concluded that the repeated inhalation of endotoxins induces in rabbits a state of hypersensitivity and at the same time the appearance of inflammatory reactions in the bronchi and alterations in the mechanical properties of the lung. These changes may be significant in the pathogenesis of byssinosis.

Monitoring low benzene exposure : comparative evaluation of urinary biomarkers, influence of cigarette smoking and genetic polymorphisms

Benzene is a human carcinogen and an ubiquitous environmental pollutant. Identification of specific and sensitive biological markers is critical for the definition of exposure to low benzene level and the evaluation of the health risk posed by this exposure. This investigation compared urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid, and benzene (U-benzene) as biomarkers to assess benzene exposure and evaluated the influence of smoking and the genetic polymorphisms CYP2E1 (RsaI and DraI) and NADPH quinone oxidoreductase-1 on these indices. Gas station attendants, urban policemen, bus drivers, and two groups of controls were studied (415 subjects). Median benzene exposure was 61, 22, 21, 9 and 6 μg/m3, respectively, with higher levels in workers than in controls. U-benzene, but not t,t-MA and S-phenylmercapturic acid, showed an exposure-related increase. All the biomarkers were strongly influenced by cigarette smoking, with values up to 8-fold higher in smokers compared with nonsmokers. Significant correlations of the biomarkers with each other and with urinary cotinine were found. A possible influence of genetic polymorphism of CYP2E1 (RsaI and/or DraI) on t,t-MA and U-benzene in subjects with a variant allele was found. Multiple linear regression analysis correlated the urinary markers with exposure, smoking status, and CYP2E1 (RsaI; R2 up to 0.55 for U-benzene). In conclusion, in the range of investigated benzene levels (<478 μg/m3 or <0.15 ppm), smoking may be regarded as the major source of benzene intake; among the study indices, U-benzene is the marker of choice for biomonitoring low-level occupational and environmental benzene exposure.

Occupational exposure to polychlorinated biphenyls in electrical workers. II. Health effects.

Health conditions were evaluated in 80 electrical workers exposed for many years to polychlorinated biphenyl (PCB) mixtures with a 42% mean chlorine content, who had blood PCB concentrations from 41 to 1319 micrograms/kg. The clinical study was based on personal history data, physical examination, and laboratory tests (red cell and leukocyte count; determination of haemoglobin, packed cell volume, bilirubin, serum protein electrophoretic fractions, pseudocholinesterase, AST, ALT, GGT, and OCT). Fifteen workers were found to have skin diseases--chloracne (4), folliculitis (4), oil dermatitis (1), juvenile acne (1), and dermatitis due to irritative or allergic agents (5). Sixteen workers showed more or less pronounced hepatic involvement, consisting most often of hepatomegaly with an increase in serum GGT, AST, ALT, and OCT values. In two workers bleeding cavernous haemangiomas were discovered, in one case associated with chronic myelocytic leukaemia. All the workers with chloracne were employed on electric capacitor impregnation with PCBs, and no definite association was found between chloracne and blood PCB concentrations. Conversely, a significant positive association was found between the abnormal liver findings and blood PCB concentrations, particularly trichlorobiphenyl blood concentrations. The abnormal hepatic findings observed are similar to those reported in experimental animals given PCBs, and in some workers such findings should probably be considered as clinical signs of hepatic microsomal enzyme induction.

Occupational triphenyltin acetate poisoning: a case report

A case of triphenyltin acetate (TPTA) poisoning is described. The patient, who had been exposed mainly to cutaneous absorption, showed acute stages of an urticarial eruption, signs of hepatic injury, slight glucose intolerance, and electroencephalographic abnormalities. Concomitant with the highest concentrations of tin in plasma and the peak of tin excretion in urine, neutrophils did not show the normal increase in actin polymerisation after stimulation with a chemotactic peptide (100 nM fMLP). The peak of urinary excretion of tin occurred between the fifth and the sixth day after poisoning; subsequently, the rate of excretion became slow, suggesting biphasic kinetics with the possibility of a cumulative trend.

Toxicological and immune findings in workers exposed to Pentachlorophenol (PCP)

Pentachlorophenol (PCP) is a pesticide used worldwide in industrial and domestic applications. Data available on the effects of technical-grade PCP on the immune system are insufficient and equivocal; some data indicate inhibitory effects, whereas others suggest stimulating effects. This study was performed to evaluate toxicological and immune findings in 32 subjects who had prolonged exposure to PCP in a wood factory and in 37 controls. PCP concentrations were determined in plasma and urine of all subjects. Lymphocyte subsets of CD3-, CD4-, and CD8-positive cells were evaluated, and the proliferative response of peripheral blood mononuclear cells (PBM) to mitogens was assessed. The results suggested the absence of major laboratory and clinical signs of PCP-dependent immune deficiency. A weak effect of long-term exposure to PCP on the functional immune response could not be ruled out because of the finding of a decreased response to 5% PHA in the high-exposure group. A weak effect against hepatocyte membrane was evidenced by the finding of raised serum concentration of glycocholic, taurodeoxycholic, and glycochenodeoxycholic acids in subjects directly exposed to PCP for more than 10 y.

Occupational exposure to polychlorinated biphenyls in electrical workers. I. Environmental and blood polychlorinated biphenyls concentrations.

Industrial exposure to polychlorinated biphenyls (PCBs) and internal dose were investigated in 80 worker exposed for many years to PCB mixtures with a 42% chlorine content (Pyralene 3010 and Apirolio). PCBs were determined by liquid gas chromatography on samples taken from workroom air, workroom surfaces and tools, the palms of the hand, and the blood of the workers. In the workroom air samples, PCB concentrations ranged from 48 to 275 micrograms/m3. All tested surfaces and tools were heavily contaminated, with a range from 0.2 to 159 micrograms PCBs per cm2 of surface. Considerable amounts of PCBs were detected on the palms of the hands of the workers (2-28 microgram/cm2 of skin surface). In blood, total PCB concentrations from 88 to 1319 micrograms/kg were observed: comparing the blood concentrations of low and high chlorine content biphenyls, a significant difference was found for the low-chlorinated biphenyl concentrations between workers currently exposed and workers exposed only in the past. In groups of workers who were homogeneous as regards work area and job, the PCB concentrations in the blood were closely correlated with the length of actual occupational exposure to these compounds. These findings led to the conclusion that absorption of PCBs in these workers had occurred mainly through the skin, therefore industrial preventive surveillance must take this route of exposure into account. Since blood PCB concentrations appear to be correlated with the length of exposure, PCB determination on whole blood may be used to monitor industrial and environmental exposure to PCBs.

Immunomodulatory effects of occupational exposure to mancozeb.

The effects of occupational exposure to ethylene-bis-dithiocarbamate of manganese and zinc on the immune system were evaluated in a group of mancozeb-exposed manufacturers and controls. The immune system tests revealed the following: (a) lymphocyte proliferative responses triggered by different activators and mitogen-induced IL-2 production were higher in exposed subjects than in controls; (b) production of monocyte/macrophage-derived IL-1 and polyclonal IgG and IgM, by beta-lymphocytes, did not differ between exposed subjects and controls; (c) percentages and absolute numbers of total T-cells, T-helper cells, T-suppressor/cytotoxic cells, activated T-cells, total beta-cells, and natural killer cells were similar in exposed subjects and controls; (d) serum immunoglobulin classes and complement fractions were within the range of normality; and (e) rheumatoid factor and non-organ-specific serum autoantibodies were absent in exposed and control subjects. An increase in T-cell functional response was found in the exposed group, suggesting a slight immunomodulator effect of mancozeb in conditions of low-level, prolonged occupational exposure.

Urinary hydroxylated metabolites of polycyclic aromatic hydrocarbons as biomarkers of exposure in asphalt workers

Abstract Background. Fumes and vapours released during laying of hot asphalt mix have been recognised as a major source of exposure for asphalt workers. Objectives. We investigated the relationships between inhalation exposure to asphalt emissions and urinary biomarkers of polycyclic aromatic hydrocarbons (PAHs) in asphalt workers (AW, n=75) and in ground construction workers (CW, n=37). Methods. Total polyaromatic compounds (PAC) and 15 priority PAHs in inhaled air were measured by personal sampling. Hydroxylated PAH metabolites (OH-PAHs) (2-naphthol, 2-hydroxyfluorene, 3-hydroxyphenanthrene, 1-hydroxypyrene, 6-hydroxychrysene and 3-hydroxybenzo[a]pyrene) were determined in urine spot samples collected in three different times during the work week. Results. Median vapour-phase PAC (5.5 µg m–3), PAHs (≤50 ng m–3) and OH-PAHs (0.08–1.11 µg l–1) were significantly higher in AW than in CW, except in the cases of air naphthalene and 2-naphthol. Airborne levels of particle-phase contaminants were similar in the two groups and much lower than vapour-phase levels; metabolites of particulate PAHs were never found in quantifiable amounts. An appreciable increase in OH-PAH levels during the work day and work week was found in AW; median levels for 2-hydroxyfluorene, 3-hydroxyphenanthrene and 1-hydroxypyrene were, respectively, 0.29, 0.08 and 0.18 at baseline; 0.50, 0.18 and 0.29, pre-shift; 1.11, 0.44 and 0.44 µg l–1, post-shift. Each OH-PAH exhibited a characteristic profile of increase, reflecting differences in half-lives of the parent compounds. In non-smoking subjects, positive correlations were found between vapour-phase PAC or PAHs and OH-PAHs both in pre- and post-shift samples (0.34 ≤ r≤69). Smokers exhibited 2–5-fold higher OH-PAHs than non-smokers, at any time and at both workplaces. Conclusions. Our results suggest that OH-PAHs are useful biomarkers for monitoring exposure to asphalt emissions. The work-related exposure to PAC and PAHs was low in all AW, but urinary metabolites reflected exposure satisfactorily.

Evaluation of Exposure to PAHs in Asphalt Workers by Environmental and Biological Monitoring

Abstract:  In the present article we assessed exposure to polycyclic aromatic hydrocarbons (PAHs) in Italian asphalt workers (AW, n= 100), exposed to bitumen fumes and diesel exhausts, and in roadside construction workers (CW, n= 47), exposed to diesel exhausts, by means of environmental and biological monitoring. 1‐Hydroxypyrene (OH‐Py) was determined in urine spot samples collected, respectively, after 2 days of vacation (baseline), before, and at the end of the monitored work shift, in the second part of the workweek. Median airborne levels during the work shift of 15 PAHs (both vapor and particulate phases), from naphthalene (NAP) to indeno(1,2,3‐cd)pyrene, ranged from below 0.03 to 426 ng/m3. Median excretion values of OH‐Py in baseline, before‐ and end‐shift samples were 228, 402, and 690 ng/L for AW and 260, 304, and 378 ng/L for CW. Lower values were found in nonsmokers compared to smokers (e.g., in AW 565 and 781 versus 252 and 506 ng/L in before‐shift and end‐shift samples, respectively). In all subjects a weak correlation between personal exposure to the sum of airborne 15 PAHs and OH‐Py was observed (r= 0.30). The results of this article show that AW experienced a moderate occupational exposure to airborne PAHs, resulting in a significant increase of urinary OH‐Py during the workday and the workweek. The contribution of working activities to internal dose was in the same order of magnitude of the contribution of cigarette smoking.