Luciano Romeo

Occupational Exposure to Solvents and the Risk of Lymphomas

Background: A number of studies have shown possible associations between occupational exposures, particularly solvents, and lymphomas. The present investigation aimed to evaluate the association between exposure to solvents and lymphomas (Hodgkin and non-Hodgkin) in a large population-based, multicenter, case–control study in Italy. Methods: All newly diagnosed cases of malignant lymphoma in men and women age 20 to 74 years in 1991–1993 were identified in 8 areas in Italy. The control group was formed by a random sample of the general population in the areas under study stratified by sex and 5-year age groups. We interviewed 1428 non-Hodgkin lymphoma cases, 304 Hodgkin disease cases, and 1530 controls. Experts examined the questionnaire data and assessed a level of probability and intensity of exposure to a range of chemicals. Results: Those in the medium/high level of exposure had an increased risk of non-Hodgkin lymphoma with exposure to toluene (odds ratio = 1.8; 95% confidence interval = 1.1–2.8), xylene 1.7 (1.0–2.6), and benzene 1.6 (1.0–2.4). Subjects exposed to all 3 aromatic hydrocarbons (benzene, toluene, and xylene; medium/high intensity compared with none) had an odds ratio of 2.1 (1.1–4.3). We observed an increased risk for Hodgkin disease for those exposed to technical solvents (2.7; 1.2–6.5) and aliphatic solvents (2.7; 1.2–5.7). Conclusion: This study suggests that aromatic and chlorinated hydrocarbons are a risk factor for non-Hodgkin lymphomas, and provides preliminary evidence for an association between solvents and Hodgkin disease.

Breath and blood levels of benzene, toluene, cumene and styrene in non-occupational exposure

SummaryBenzene, toluene, cumene and styrene were measured in the breath and blood of two groups of individuals. The first group included individuals belonging to a hospital staff, the second group included chemical workers who were not exposed to the abovementioned chemicals. The chemical workers were examined in plant infirmaries on the morning before the start of the workshift, and the hospital staff in the hospital infirmaries. One environmental air sample was taken in the infirmaries for each individual at the moment of the biological samplings. The environmental concentrations of benzene and styrene were significantly higher in the infirmaries of the chemical plant than in the infirmaries of the hospital. On the other hand, the environmental concentrations of toluene and cumene were not significantly different in the plant infirmaries and in the hospital infirmaries. In the hospital staff the alveolar concentrations of benzene, toluene and styrene were significantly lower than those in the chemical workers. In the hospital staff the blood concentrations of benzene, toluene and styrene were not significantly different from those in the chemical workers. Only the blood cumene concentration was significantly higher in the chemical workers. In hospital staff, smokers showed alveolar and blood concentrations of benzene and toluene that were significantly higher than those measured in the non smoker hospital staff. With reference to chemical workers, only alveolar benzene concentration was significantly higher in smokers than in non smokers. A significant blood benzene difference was found between the non smoker hospital staff and the non smoker chemical workers. A correlation between alveolar and environmental concentrations was found for benzene, toluene and cumene, but not for styrene. In the two groups of individuals, correlations between blood and alveolar concentrations of the four compounds were also studied.

Reference values for blood benzene in the occupationally unexposed general population.

SummaryBlood benzene was determined by gas chromatography-mass spectrometry in 431 “normal” subjects, subdivided into 155 rural subjects and 276 urban subjects. Blood benzene (mean value 262 ng/l) was significantly lower in rural (200 ng/l) than in urban (296 ng/l) workers, as well as differing significantly between 293 non-smokers and 138 smokers (205 ng/l and 381 ng/l, respectively). Among non-smokers, values were significantly higher (307 ng/l) in 76 chemical workers. In the total study population, in 95% of cases blood benzene was less than 718 ng/l, the 95th percentile being 514 ng/l in non-smokers vs 901 ng/l in smokers and 576 ng/l in rural vs 822 ng/l in urban subjects. Within each population subgroup, the difference between non-smokers and smokers was statistically significant, except among office workers (non-smokers 234 ng/l, smokers 304 ng/l). Blood benzene (y) was directly proportional to the number of cigarettes smoked (x) (y = 201 + 12x; r = 0.44; n = 431), and inversely proportional to the interval between the last cigarette and the time at which the blood sample was taken (z) (log y = 6.167 − 0.0015 z; r = −0.461; n = 135). The blood half-life of benzene was about 8h. The multiple correlation between blood benzene (Cb), number of cigarettes per day (x) and time since the last cigarette (z) is: Cb = 417 + 7.2x − 0.41z (n = 135; R = 0.20; P < 0.00001).

Risk of leukemia and multiple myeloma associated with exposure to benzene and other organic solvents: Evidence from the Italian Multicenter Case–control study

BACKGROUND While there is a general consensus about the ability of benzene to induce acute myeloid leukemia (AML), its effects on chronic lymphoid leukemia and multiple myeloma (MM) are still under debate. We conducted a population-based case-control study to evaluate the association between exposure to organic solvents and risk of myeloid and lymphoid leukemia and MM. METHODS Five hundred eighty-six cases of leukemia (and 1,278 population controls), 263 cases of MM (and 1,100 population controls) were collected. Experts assessed exposure at individual level to a range of chemicals. RESULTS We found no association between exposure to any solvent and AML. There were elevated point estimates for the associations between medium/high benzene exposure and chronic lymphatic leukemia (OR = 1.8, 95% CI = 0.9-3.9) and MM (OR = 1.9, 95% CI = 0.9-3.9). Risks of chronic lymphatic leukemia were somewhat elevated, albeit with wide confidence intervals, from medium/high exposure to xylene and toluene as well. CONCLUSIONS We did not confirm the known association between benzene and AML, though this is likely explained by the strict regulation of benzene in Italy nearly three decades prior to study initiation. Our results support the association between benzene, xylene, and toluene and chronic lymphatic leukemia and between benzene and MM with longer latencies than have been observed for AML in other studies.

Metabolism of arsenic after acute occupational arsine intoxication

Among the elements of toxicological relevance, inorganic arsenic (As) probably exhibits the most complex metabolism, and we deemed it interesting to identify and quantify the different As species excreted after an occupational acute intoxication with arsine. For this purpose total As and five As species were determined using an hybrid analytical method coupling liquid chromatography with inductively coupled plasma mass spectrometry. The highest urinary elimination of total As was observed in the first 5 d after admission. The As species mostly excreted were monomethylarsonate (MMA), dimethylarsinate (DMA), As3+, arsenobetaine (AsB), and to a lesser extent As5+. The amount of AsB excreted in urine by the subject does not appear to be completely justified by AsB intake through food. Arsenic is excreted mainly via the urine with a clearance of 7.8 ml/h/kg and follows a triphasic model with periods of 28 h, 59 h, and 9 d, respectively. The evidence that DMA excretion culminates after a few days, when the excretion of the inorganic form is substantially reduced (while that of MMA is still elevated), seems to confirm the existence of two successive methylating enzyme activities. Furthermore, the elimination rate of As from blood follows a three-phase model and the half-lives of different species vary from about 27 to 86 h with the following gradient As5+ < MMA < As3+ < DMA < AsB.

Blood styrene concentrations in a “normal” population and in exposed workers 16 hours after the end of the workshift

SummaryBlood styrene was measured by a gas chromatography-mass spectrometry method in 81 “normal people” and in 76 workers exposed to styrene. In the normal subjects, styrene was also tested in alveolar and environmental air. Styrene was found in nearly all (95%) blood samples. Average styrene levels in the normal subjects were 221 ng/1 in blood (Cb), 3 ng/1 in alveolar air (Ca) and 6 ng/1 in environmental air (Ci). Styrene levels did not differ significantly between smokers and non-smokers, 95% of values being below 512 ng/1 in Cb, 7 ng/1 in Ca and 15 ng/l in Ci. In workers with an average exposure to styrene of 204 μg/l, at the end of the workshift, mean blood styrene concentration was 1211 μg/l. In blood samples collected at the end of the Thursday shift, styrene levels were significantly higher (1590 μg/1) than those found at the end of the Monday shift (1068 μg/l. A similar difference was found in samples taken the morning after exposure (60 and 119 μg/l, respectively). Significant correlations between blood and environmental styrene were found both at the end of the shift and the morning after exposure (r=0.61 and 0.41, respectively). In workers occupationally exposed to styrene, 16 h after the end of the workshift, blood styrene (94 μg/l) was significantly higher than that found in the normal subjects (0.22 μg/l). The half-life of blood styrene was 3.9 h.

Exposure to mutagenic airborne particulate in a rubber manufacturing plant.

Epidemiological studies conducted in the 1980s revealed that people working in the rubber manufacturing industry had an increased risk of cancer. Even now, workers employed in rubber processing are still at risk despite the measures adopted to improve their working conditions. The aim of the study was to evaluate the presence of a genotoxic risk in a rubber industry and to verify whether or not it was possible to locate the most dangerous position among the different rubber-working processes. The mutagenic activity of airborne particulate was evaluated in samples collected in the mixing department of a rubber manufacturing plant. Ambient air samples were taken over 3-h period in two stable positions near the mixing (Banbury mixer) and calendering areas. Personal air samples were taken over 2-h period during a normal workday from five workers employed in different rubber processing operations (mixing, weighing, calendering, compounding and extruding). The mutagenic activity of the air samples was determined by plate incorporation assay using Salmonella typhimurium strains (TA 98, TA 98NR, TA 100, YG 1021) with and without metabolic activation. Polycyclic aromatic hydrocarbon (PAH) concentrations were determined by high-performance liquid chromatography (HPLC); the presence of other presumable contaminants were carried out by gas chromatography-mass spectrometry (GC-MS). The results showed substantial direct and indirect frameshift mutagenicity in both ambient and personal samples. No mutagenic activity was present in S. typhimurium TA 100, except in the personal sample from a worker employed on the Banbury mixer. HPLC analysis revealed very low concentrations of PAHs. GC-MS analysis showed the presence of compounds such as azulene derivative, 1,2-dihydro-2,2,4-trimethylquinoline, N-methyl N-phenylbenzenamine, diphenylamine, bis(2-ethylhexyl)phthalate and bis(methyl-propyl)phthalate. We conclude that the high levels of mutagenic activity in ambiental and personal samples indicate the presence of substances with high genotoxic potency; no substantial differences were seen among the several rubber processing operations. PAHs were not involved in indoor pollution. GC-MS analysis revealed the presence of compounds which may be produced by high temperatures to which the raw materials are subjected during rubber manufacturing processes. These substances are potential carcinogen though their mutagen properties have not been clearly determined.

Effects of lead on red blood cell membrane proteins

SummaryThe effects of lead on red blood cell (RBC) membrane proteins were studied in two groups of workers with different lead exposure levels: Group 1 (6 subjects employed in a battery plant) with a mean blood lead of 40.1 (SD = 3.7) μg/100 ml; Group II(5 workers employed in different industries) with a mean blood lead of 60.6 (SD = 8.0) μg/100 ml, compared with a control group with mean blood lead of 15.6 (SD = 9.3) μg/100 ml. The analysis of RBC membrane polypeptides was carried out by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and by using a densitometer for percentage measurement of the bands corresponding to protein fractions. The results show a very significant decrease in Band 3 (anion channel) and 4.1 in more exposed workers (Group II) only. The effects of lead on RBC membrane proteins seem to be evident at blood-lead levels higher (> 50 μg/100 ml) than those previously reported in literature. These results confirm the effects of lead on membrane proteins, even if the exact mechanism, particularly the influence of proteolysis and the meaning of the interference, still needs to be investigated thoroughly.

Respiratory Health Effects and Immunological Response to Thermoactinomyces among Sugar Cane Workers in Nicaragua

Abstract Specific sensitization and respiratory effects associated with the inhalation of sugar cane dust were evaluated in a group of 51 Nicaraguan workers exposed to bagasse. A questionnaire interview, lung function test, serum precipitin tests for Thermoactinomyces sacchari and T. vulgaris, and immunoglobulin E tests for specific environmental allergens were performed for each worker. Twenty-one workers reported at least one respiratory symptom and 16 reported possible symptoms of bagassosis. Six workers demonstrated acute symptoms, 1 had chronic symptoms, and 9 had the reacutized form of the disease. A higher proportion of precipitin response to T. sacchari and T. vulgaris was found in workers reporting symptoms suggestive of acute bagassosis. A possible restrictive ventilatory pattern was observed in 8 subjects and a mild airway obstruction in 1 subject. Priority must be given to a surveillance and exposure prevention program for workers employed in sugar cane production and processing.

Ubiquitous pollution by n-hexane and reference biological levels in the general population.

Summaryn-Hexane levels were determined by gas chromatography and mass spectrometry in environmental air and in the alveolar air, blood and urine of a group of subjects aged on average of 38 years who had not been occupationally exposed to this hydrocarbon. n-Hexane was found in all environmental air samples examined (n=49), with the mean concentration being 104 ng/l (limit values, 1–279 ng/l). It was also found in all 49 samples of alveolar air, with the mean concentration being 50 ng/l (variation limit, 1–304ng/l). In 64 samples of urine, n-hexane was found in only 50 samples, with the mean concentration being 1,417 ng/l (limit values, 34–8,820 ng/l). In 77 of the 90 blood samples taken, a mean concentration of 608 ng/l was detected (variation limit, 15–7,684ng/l). Particularly the haematic and urinary concentration showed significant differences among the nine groups of individuals classified according to their work activity. The lowest levels were found in the blood and urine of farmers: 270 and 298 ng/l, respectively. The highest values were found for chemical workers (1,377 and 411 ng/1), respectively printers (585 and 2,691 ng/l respectively), and traffic wardens (740 and 8,820 ng/l, respectively). In all, 95% of the determinations of n-hexane yielded values of < 255 ng/l in environmental samples, < 105 ng/l in alveolar air, < 1,475 ng/l in blood and < 5,875 ng/l in urine. A comparison of these data revealed a significant correlation between environmental levels and alveolar (r/s = 0.769; P<0.00001), haematic (r/s = 0.624; P<0.0002), and urinary (r/s = 0.597; P<0.0005) values for n-hexane.