Formaldehyde and Acetaldehyde Exposure in "Non-Traditional" Occupational Sectors: Bakeries and Pastry Producers.

INTRODUCTION: Formaldehyde, a colorless and highly irritating substance, causes cancer of the nasopharynx and leukemia. Furthermore, it is one of the environmental mutagens to which humans are most abundantly exposed. Acetaldehyde was recently classified as carcinogen class 1B and mutagen class 2 in Annex VI EC regulation. Occupational exposure to the two aldehydes occurs in a wide variety of occupations and industries. The aim of this study is to deepen exposure to the two aldehydes in the non-traditional productive sectors of bakeries and pastry producers. METHODS: The evaluation of exposure to formaldehyde and acetaldehyde was conducted in Italy in 2019, in specific tasks and positions of 11 bakeries and pastry producers (115 measures, of which 57.4% were in fixed positions and the rest were personal air sampling). The measurements were performed using Radiello© radial diffusion samplers. A logarithmic transformation of the data was performed, and the correlation between the two substances was calculated. Moreover, linear models considering the log-formaldehyde as the outcome and adjusting for log-acetaldehyde values were used. RESULTS: The study identified high levels of acetaldehyde and formaldehyde exposure in the monitored workplaces. Higher mean values were observed in the leavening phase (8.39 µg/m3 and 3.39 µg/m3 for log-transformed data acetaldehyde and formaldehyde, respectively). The adjusted univariate analyses show statistically significant factors for formaldehyde as the presence of yeast, the presence of type 1 flour, the use of barley, the use of fats, the type of production, the use of spelt, and the presence of type 0 flour. CONCLUSIONS: The measurements confirmed the release of formaldehyde and acetaldehyde in bakeries and pastry industries, especially in some phases of the work process, such as leavening.

Italian pool of asbestos workers cohorts: asbestos related mortality by industrial sector and cumulative exposure.

OBJECTIVE: Italy has been a large user of asbestos and asbestos containing materials until the 1992 ban. We present a pooled cohort study on long-term mortality in exposed workers. METHODS: Pool of 43 Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding, glasswork, harbors, insulation and other industries). SMRs were computed by industrial sector for the 1970-2010 period, for the major causes, using reference rates by age, sex, region and calendar period. RESULTS: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Asbestos exposure was estimated at the plant and period levels. Asbestos related mortality was significantly increased. All industrial sectors showed increased mortality from pleural malignancies, and most also from peritoneal and lung cancer and asbestosis, with exposure related trend. Increased mortality was also observed for ovarian cancer and for bladder cancer. DISCUSSION: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. A large increase in mortality from asbestosis was observed.

Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.

OBJECTIVES: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis. METHODS: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time. RESULTS: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer. CONCLUSIONS: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.

Italian pool of asbestos workers cohorts: mortality trends of asbestos-related neoplasms after long time since first exposure.

OBJECTIVE: Asbestos is a known human carcinogen, with evidence for malignant mesothelioma (MM), cancers of lung, ovary, larynx and possibly other organs. MM rates are predicted to increase with a power of time since first exposure (TSFE), but the possible long-term attenuation of the trend is debated. The asbestos ban enforced in Italy in 1992 gives an opportunity to measure long-term cancer risk in formerly exposed workers. METHODS: Pool of 43 previously studied Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding), with mortality follow-up updated to 2010. SMRs were computed for the 1970â€"2010 period, for the major causes, with consideration of duration and TSFE, using reference rates by age, sex, region and calendar period. RESULTS: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Mortality was significantly increased for all deaths (SMR: men: 1.05, 95% CI 1.03 to 1.06; women: 1.17, 95% CI to 1.12 to 1.22), all malignancies combined (SMR: men: 1.17, 95% CI to 1.14 to 1.20; women: 1.33, 95% CI 1.24 to 1.43), pleural and peritoneal malignancies (SMR: men: 13.28 and 4.77, 95% CI 12.24 to 14.37 and 4.00 to 5.64; women: 28.44 and 6.75, 95% CI 23.83 to 33.69 and 4.70 to 9.39), lung (SMR: men: 1.26, 95% CI 1.21 to 1.31; women: 1.43, 95% CI 1.13 to 1.78) and ovarian cancer (SMR=1.38, 95% CI 1.00 to 1.87) and asbestosis (SMR: men: 300.7, 95% CI 270.7 to 333.2; women: 389.6, 95% CI 290.1 to 512.3). Pleural cancer rate increased during the first 40 years of TSFE and reached a plateau after. DISCUSSION: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. Pleural cancer mortality reached a plateau at long TSFE, coherently with recent reports.

Reference rates for cohort studies in Italy: an essential tool in occupational and residential cohort studies. / Aggiornamento dei tassi di mortalità in Italia, strumento fondamentale per la conduzione di studi di coorte occupazionali e residenziali.

The cohort study aims to test the hypothesis of an association between specific exposure/s and adverse health outcomes. The cohorts include the subjects who experience the exposure/s and are followed up over time to ascertain the health outcomes. This contribution presents the database for the analysis of mortality studies which is made available for public institutions carrying out cohort studies in Italy. The rates were computed from official mortality data from ISTAT. The database contains 141 causes or groups of causes for the years 1970-2012 ensuring correspondence with subsequent editions of ICD (International Classification of Diseases) VIII, IX and X.

[Time trend in mesothelioma and lung cancer risk in asbestos workers in Italy]. / Valutazione della variazione temporale del rischio di mesotelioma e di tumore del polmone nelle coorti di esposti ad amianto per lavoro in Italia.

This study aims at investigating, in asbestos exposed workers, the time trend of their risk of mesothelioma and of other neoplasm after very long latency and after the cessation of asbestos exposure. We pooled a large number of Italian cohorts of asbestos workers and updated mortality follow-up. The pool of data for statistical analyses includes 51,988 workers, of which 6,058 women: 54.2% was alive at follow-up, 42.6% was dead, and 2.8%was lost. Cause of death is known for 94.3%: 2,548 deaths from lung cancer, 748 frompleural cancer, 173 fromperitoneal cancer, and 434 from asbestosis. An exposure index is being developed to compare the different cohorts. Data analysis is in progress. This study will have the size for analysing not only time trends in mesothelioma, but also the occurrence of rarer diseases and cancer specific mortality in women.

Road Traffic Pollution and Childhood Leukemia: A Nationwide Case-control Study in Italy.

BACKGROUND: The association of childhood leukemia with traffic pollution was considered in a number of studies from 1989 onwards, with results not entirely consistent and little information regarding subtypes. AIM OF THE STUDY: We used the data of the Italian SETIL case-control on childhood leukemia to explore the risk by leukemia subtypes associated to exposure to vehicular traffic. METHODS: We included in the analyses 648 cases of childhood leukemia (565 Acute lymphoblastic-ALL and 80 Acute non lymphoblastic-AnLL) and 980 controls. Information on traffic exposure was collected from questionnaire interviews and from the geocoding of house addresses, for all periods of life of the children. RESULTS: We observed an increase in risk for AnLL, and at a lower extent for ALL, with indicators of exposure to traffic pollutants. In particular, the risk was associated to the report of closeness of the house to traffic lights and to the passage of trucks (OR: 1.76; 95% CI 1.03-3.01 for ALL and 6.35; 95% CI 2.59-15.6 for AnLL). The association was shown also in the analyses limited to AML and in the stratified analyses and in respect to the house in different period of life. CONCLUSIONS: Results from the SETIL study provide some support to the association of traffic related exposure and risk for AnLL, but at a lesser extent for ALL. Our conclusion highlights the need for leukemia type specific analyses in future studies. Results support the need of controlling exposure from traffic pollution, even if knowledge is not complete.

Childhood leukemia and 50 Hz magnetic fields: findings from the Italian SETIL case-control study.

We report on an Italian case-control study on childhood leukemia and exposure to extremely low frequency magnetic fields (ELF-MF). Eligible for inclusion were 745 leukemia cases, aged 0-10 years at diagnosis in 1998-2001, and 1475 sex- and age-matched population controls. Parents of 683 cases and 1044 controls (92% vs. 71%) were interviewed. ELF-MF measurements (24-48 h), in the child's bedroom of the dwelling inhabited one year before diagnosis, were available for 412 cases and 587 controls included in the main conditional regression analyses. The magnetic field induction was 0.04 µT on average (geometric mean), with 0.6% of cases and 1.6% of controls exposed to >0.3 µT. The impact of changes in the statistical model, exposure metric, and data-set restriction criteria was explored via sensitivity analyses. No exposure-disease association was observed in analyses based on continuous exposure, while analyses based on categorical variables were characterized by incoherent exposure-outcome relationships. In conclusion, our results may be affected by several sources of bias and they are noninformative at exposure levels >0.3 µT. Nonetheless, the study may contribute to future meta- or pooled analyses. Furthermore, exposure levels among population controls are useful to estimate attributable risk.

SETIL: Italian multicentric epidemiological case-control study on risk factors for childhood leukaemia, non hodgkin lymphoma and neuroblastoma: study population and prevalence of risk factors in Italy.

BACKGROUND: Aetiology of childhood leukaemia and childhood neoplasm is poorly understood. Information on the prevalence of risk factors in the childhood population is limited. SETIL is a population based case-control study on childhood leukaemia, conducted with two companion studies on non-Hodgkin Lymphoma (NHL) and neuroblastoma. The study relies on questionnaire interviews and 50 Hz magnetic field (ELF-MF) indoor measurements. This paper discusses the SETIL study design and includes descriptive information. METHODS: The study was carried out in 14 Italian regions (78.3% of Italian population aged 0-10). It included leukaemia, NHL and neuroblastoma cases incident in 0-10 year olds in 1998-2001, registered by the Italian Association of Paediatric Haematology and Oncology (AIEOP) (accrual over 95% of estimated incidence). Two controls for each leukaemia case were randomly sampled from the Local Health Authorities rolls, matched by gender, birthdate and residence. The same controls were used in NHL and neuroblastoma studies. Parents were interviewed at home on: physical agents (ELF-MF and ionizing radiation), chemicals (smoking, solvents, traffic, insecticides), occupation, medical and personal history of children and parents, infectious diseases, immunizations and associated factors. Occupational exposure was collected using job specific modules. ELF-MF was measured in the main rooms (spot measurement) and close to child's bed (48 hours measurement). RESULTS: The study included: 683 leukaemia cases (87% ALL, 13% AnLL), 97 NHL, 155 neuroblastomas, and 1044 controls. CONCLUSIONS: SETIL represents a data source on exposure of Italian children to a broad array of potential carcinogenic factors.

Tobacco smoke and risk of childhood acute non-lymphocytic leukemia: findings from the SETIL study.

BACKGROUND: Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS) as risk factors for Acute non-Lymphocytic Leukemia (AnLL) were investigated. METHODS: Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998-2001. We estimated odds ratios (OR) and 95% confidence intervals (95%CI) conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene. RESULTS: Paternal smoke in the conception period was associated with AnLL (OR for ≥ 11 cigarettes/day  = 1.79, 95% CI 1.01-3.15; P trend 0.05). An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day  = 1.85, 95%CI 0.97-3.52; P trend 0.07). No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS. CONCLUSIONS: This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates.

Risk of neuroblastoma, maternal characteristics and perinatal exposures: the SETIL study.

PURPOSE: Neuroblastoma (NB) is the most common extra-cranial paediatric solid tumour. Incidence peaks in infancy, suggesting a role of in-utero and neonatal exposures but its aetiology is largely unknown. The aim of the present study is to evaluate the association between maternal characteristics and perinatal factors with the risk of NB, using data from the SETIL database. METHODS: SETIL is a large Italian population-based case-control study established to evaluate several potential cancer risk factors in 0-10 year olds. Information about maternal characteristics, reproductive history, environmental and occupational exposures during pregnancy, as well as newborns' characteristics were obtained using a structured questionnaire. Extremely low frequency magnetic field (ELF-MF) home exposure was measured. The study included 1044 healthy controls and 153 NB cases, diagnosed between 1998 and 2001. RESULTS: A twofold risk was associated to exposure in pregnancy to chemical products for domestic work and to hair dye. The risk associated with the latter was higher among 0-17 month old children (OR = 5.5, 95%CI: 1.0-29.3). Risk was increased for children whose mothers had suffered work related exposure in the preconception period to solvents (OR = 2.0 95%CI: 1.0-4.1) and in particular to aromatic hydrocarbons (OR = 9.2, 95%CI: 2.4-34.3). No association was observed with ELF-MF exposure. A higher risk was found among children with congenital malformations (OR = 4.9, 95%CI: 1.8-13.6) or neurofibromatosis (2 cases and 0 controls, p = 0.016). CONCLUSIONS: Our study suggests maternal exposure to hair dyes and aromatic hydrocarbons plays a role and deserves further investigation. The association with congenital malformations might also be explained by over-diagnosis. External exposure, in particular during and before pregnancy might contribute to NB occurrence.

Tobacco smoke and risk of childhood acute lymphoblastic leukemia: findings from the SETIL case-control study.

PURPOSE: Tobacco smoke could cause childhood acute lymphoblastic leukemia (ALL) through at least three pathways: (1) prenatal parental smoking; (2) fetal exposure through maternal smoking during pregnancy; and (3) childhood exposure to secondhand smoke (SHS). We tested these hypotheses in a large population-based case-control study (SETIL) primarily designed to evaluate the role of electromagnetic fields in childhood hematopoietic malignancies. METHODS: From 1998 to 2003, we enrolled 602 incident cases of ALL from 14 Italian Regions, and 918 controls were individually matched by birthdate, sex, and area of residence. Cases (n = 557) and controls (n = 855) with complete information were analyzed; odds ratios (OR) and 95 % confidence intervals (95 % CI) were estimated with logistic regression models conditioned on matching variables and adjusted by birth order, birthweight, duration of breastfeeding, parental age at delivery, education, and occupational exposure to benzene. RESULTS: No evidence associating paternal smoking in the conception period or maternal smoking during the pregnancy with ALL was found. An association of ALL with maternal exposure to SHS during pregnancy (adjusted OR for mothers exposed more than 4 h/day = 2.18, 95 % CI 1.39-3.42) was observed, but recall bias cannot be excluded. Exposure of the children to SHS was associated with ALL only in unadjusted analysis (unadjusted OR for highly exposed children = 1.64; 95 % CI 1.10-2.45). CONCLUSIONS: This study does not support the hypothesis that parental active smoking is associated with ALL. We found very weak evidence of increased risk of ALL for children exposed to SHS. Maternal exposure to SHS was associated with ALL, but recall bias is likely to inflate our estimates.

Risk of childhood leukaemia and non-Hodgkin's lymphoma after parental occupational exposure to solvents and other agents: the SETIL Study.

AIM: In the context of the Italian Multicentric Epidemiological Study on Risk Factors for Childhood Leukaemia and Non-Hodgkin's Lymphoma (SETIL), the risk of childhood cancer was investigated in relation to parental occupational exposures. METHODS: All cases of childhood leukaemia and non-Hodgkin's lymphoma (NHL) in children aged 0-10 years were identified. Controls were chosen at random from the local population in each region. Parents were interviewed using a structured questionnaire. The collected data were blindly reviewed by expert industrial hygienists in order to estimate exposure to a list of agents. Statistical analyses were performed for each agent using unconditional multivariable logistic regression models, taking into account timing of exposure. RESULTS: 683 cases of acute childhood leukaemia, 97 cases of NHL and 1044 controls were identified. Increased risk of childhood leukaemia was found for maternal exposure to aliphatic (OR 4.3) or aromatic hydrocarbons (OR 3.8) in the preconception period, and for paternal exposure to diesel exhaust (OR 1.4), lead exposure (OR 1.7) and mineral oils (OR 1.4)[corrected]. Risk of NHL appeared to be related to paternal exposure to oxygenated solvents (OR 2.5) and petrol exhaust (OR 2.2). CONCLUSIONS: We found increased risk for childhood leukaemia associated with maternal occupational exposure to aromatic and aliphatic hydrocarbons, particularly in the preconception period; increased risks were also observed for paternal exposure to diesel exhaust fumes, mineral oils and lead. The risk of NHL appeared to be related to paternal exposure to oxygenated solvent and petrol exhausts.

Exposure to benzene and childhood leukaemia: a pilot case-control study.

OBJECTIVES: Main purpose To evaluate the feasibility of a measurement-based assessment of benzene exposure in case-control studies of paediatric cancer; Additional aims To identify the sources of exposure variability; to assess the performance of two benzene biomarkers; to verify the occurrence of participation bias; to check whether exposures to benzene and to 50 Hz magnetic fields were correlated, and might exert reciprocal confounding effects. DESIGN: Pilot case-control study of childhood leukaemia and exposure to benzene assessed by repeated seasonal weekly measurements in breathing zone air samples and outside the children's dwellings, with concurrent determinations of cotinine, t-t-muconic acid (MA) and sulfo-phenylmercapturic acid (S-PMA) in urine. PARTICIPANTS: 108 cases and 194 controls were eligible for inclusion. RESULTS: Full-participation was obtained from 46 cases and 60 controls, with low dropout rates before four repeats (11% and 17%); an additional 23 cases and 80 controls allowed the collection of outdoor air samples only. The average benzene concentration in personal and outdoor air samples was 3 µg/m(3) (SD 1.45) and 2.7 µg/m(3) (SD 1.41), respectively. Personal exposure was strongly influenced by outdoor benzene concentrations, higher in the cold seasons than in warm seasons, and not affected by gender, age, area of residence or caseness. Urinary excretion of S-PMA and personal benzene exposure were well correlated. Outdoor benzene levels were lower among participant controls compared with non-participants, but did not differ between participant and non-participant cases; the direction of the bias was found to depend on the cut-point chosen to distinguish exposed and unexposed. Exposures to benzene and extremely low-frequency magnetic fields were positively correlated. CONCLUSIONS: Repeated individual measurements are needed to account for the seasonal variability in benzene exposure, and they have the additional advantage of increasing the study power. Measurement-based assessment of benzene exposure in studies of childhood leukaemia appears feasible, although it is financially and logistically demanding.