Recognition of COVID-19 with occupational origin: a comparison between European countries.

OBJECTIVES: This study aims to present an overview of the formal recognition of COVID-19 as occupational disease (OD) or injury (OI) across Europe. METHODS: A COVID-19 questionnaire was designed by a task group within COST-funded OMEGA-NET and sent to occupational health experts of 37 countries in WHO European region, with a last update in April 2022. RESULTS: The questionnaire was filled out by experts from 35 countries. There are large differences between national systems regarding the recognition of OD and OI: 40% of countries have a list system, 57% a mixed system and one country an open system. In most countries, COVID-19 can be recognised as an OD (57%). In four countries, COVID-19 can be recognised as OI (11%) and in seven countries as either OD or OI (20%). In two countries, there is no recognition possible to date. Thirty-two countries (91%) recognise COVID-19 as OD/OI among healthcare workers. Working in certain jobs is considered proof of occupational exposure in 25 countries, contact with a colleague with confirmed infection in 19 countries, and contact with clients with confirmed infection in 21 countries. In most countries (57%), a positive PCR test is considered proof of disease. The three most common compensation benefits for COVID-19 as OI/OD are disability pension, treatment and rehabilitation. Long COVID is included in 26 countries. CONCLUSIONS: COVID-19 can be recognised as OD or OI in 94% of the European countries completing this survey, across different social security and embedded occupational health systems.

Lung cancer mortality in the European cohort of titanium dioxide workers: a reanalysis of the exposure-response relationship.

OBJECTIVES: Animal bioassays have demonstrated convincing evidence of the potential carcinogenicity to humans of titanium dioxide (TiO2), but limitations in cohort studies have been identified, among which is the healthy worker survivor effect (HWSE). We aimed to address this bias in a pooled study of four cohorts of TiO2 workers. METHODS: We reanalysed data on respirable TiO2 dust exposure and lung cancer mortality among 7341 male workers employed in TiO2 production in Finland, France, UK and Italy using the parametric g-formula, considering three hypothetical interventions: setting annual exposures at 2.4 (U.S. occupational exposure limit), 0.3 (German limit) and 0 mg/m3 for 25 and 35 years. RESULTS: The HWSE was evidenced. Taking this into account, we observed a positive association between lagged cumulative exposure to TiO2 and lung cancer mortality. The estimated number of lung cancer deaths at each age group decreased across increasingly stringent intervention levels. At age 70 years, the estimated number of lung cancer deaths expected in the cohort after 35-year exposure was 293 for exposure set at 2.4 mg/m3, 235 for exposure set at 0.3 mg/m3, and 211 for exposure set at 0 mg/m3. CONCLUSION: This analysis shows that HWSE can hide an exposure-response relationship. It also shows that TiO2 epidemiological data could demonstrate an exposure-effects relationship if analysed appropriately. More epidemiological studies and similar reanalyses of existing cohort studies are warranted to corroborate the human carcinogenicity of TiO2. This human evidence, when combined with the animal evidence, strengthens the overall evidence of carcinogenicity of TiO2.

Lifetime cumulative exposure to rubber dust, fumes and N-nitrosamines and non-cancer mortality: a 49-year follow-up of UK rubber factory workers.

OBJECTIVES: To examine associations between occupational exposures to rubber dust, rubber fumes and N-nitrosamines and non-cancer mortality. METHODS: A cohort of 36 441 males aged 35+ years employed in British rubber factories was followed-up to 2015 (94% deceased). Competing risk survival analysis was used to assess risks of dying from non-cancer diseases (respiratory, urinary, cerebrovascular, circulatory and digestive diseases). Occupational exposures to rubber dust, rubber fumes, N-nitrosamines were derived based on a population-specific quantitative job-exposure matrix which in-turn was based on measurements in the EU-EXASRUB database. RESULTS: Exposure-response associations of increased risk with increasing exposure were found for N-nitrosomorpholine with mortality from circulatory diseases (subdistribution hazard ratio (SHR) 1.17; 95% CI 1.12 to 1.23), ischaemic heart disease (IHD) (SHR 1.19; 95% CI 1.13 to 1.26), cerebrovascular disease (SHR 1.19; 95% CI 1.07 to 1.32) and exposures to N-nitrosodimethylamine with respiratory disease mortality (SHR 1.41; 95% CI 1.30 to 1.53). Increased risks for mortality from circulatory disease, IHD and digestive diseases were found with higher levels of exposures to rubber dust, rubber fumes and N-nitrosamines sum, without an exposure-dependent manner. No associations were observed between rubber dust, rubber fumes and N-nitrosamines exposures with mortality from asthma, urinary disease, bronchitis, emphysema, liver disease and some digestive diseases. CONCLUSIONS: In a cohort of rubber factory workers with 49 years of follow-up, increased risk for mortality from circulatory, cerebrovascular, respiratory and digestive diseases were found to be associated with cumulative occupational exposures to specific agents.

Cancer incidence among workers with blood lead measurements in two countries.

OBJECTIVE: Study carcinogenicity of inorganic lead, classified as 'probably carcinogenic' to humans by the International Agency for Research on Cancer (brain, lung, kidney and stomach). METHODS: We conducted internal and external analyses for cancer incidence in two cohorts of 29 874 lead-exposed workers with past blood lead data (Finland, n=20 752, Great Britain=9122), with 6790 incident cancers. Exposure was maximum measured blood lead. RESULTS: The combined cohort had a median maximum blood lead of 29 µg/dL, a mean first blood lead test of 1977, and was 87% male. Significant (p<0.05) positive trends, using the log of maximum blood lead, were found for brain cancer (malignant), Hodgkin's lymphoma, lung cancer and rectal cancer, while a significant negative trend was found for melanoma. Borderline significant positive trends (0.05≤p≤0.10) were found for oesophageal cancer, meningioma and combined malignant/benign brain cancer. Categorical analyses reflected these trends. Significant interactions by country were found for lung, brain and oesophageal cancer, with Finland showing strong positive trends, and Great Britain showing modest or no trends. Larynx cancer in Finland also showed a positive trend (p=0.05). External analyses for high exposure workers (maximum blood lead >40 µg/dL) showed a significant excess for lung cancer in both countries combined, and significant excesses in Finland for brain and lung cancer. The Great Britain data were limited by small numbers for some cancers, and limited variation in exposure. CONCLUSIONS: We found strong positive incidence trends with increasing blood lead level, for several outcomes in internal analysis. Two of these, lung and brain cancer, were sites of a priori interest.

Job-exposure matrix for historical exposures to rubber dust, rubber fumes and n-Nitrosamines in the British rubber industry.

OBJECTIVES: To develop a quantitative historical job-exposure matrix (JEM) for rubber dust, rubber fumes and n-Nitrosamines in the British rubber industry for 1915-2002 to estimate lifetime cumulative exposure (LCE) for a cohort of workers with 49 years follow-up. METHODS: Data from the EU-EXASRUB database-rubber dust (n=4157), rubber fumes (n=3803) and n-Nitrosamines (n=10 115) collected between 1977 and 2002-were modelled using linear mixed-effects models. Sample year, stationary/personal measurement, industry sector and measurement source were included as fixed explanatory variables and factory as random intercept. Model estimates and extrapolations were used to construct a JEM covering all departments in both sectors of the rubber manufacturing industries for the years 1915-2002. JEM-estimates were linked to all cohort members to calculate LCE. Sensitivity analyses related to assumptions about extrapolation of time trends were also conducted. RESULTS: Changes in rubber dust exposures ranged from -6.3 %/year (crude materials/mixing) to -1.0 %/year (curing) and -6.5 %/year (crude materials/mixing) to +0.5 %/year (finishing, assembly and miscellaneous) for rubber fumes. Declines in n-Nitrosamines ranged from -17.9 %/year (curing) to -1.3 %/year (crude materials and mixing). Mean LCEs were 61 mg/m3-years (rubber dust), 15.6 mg/ m3-years (rubber fumes), 2483.2 µg/m3-years (n-Nitrosamines sum score), 18.6 µg/m3-years (N-nitrosodimethylamine) and 15.0 µg/m3-years (N-itrosomorpholine). CONCLUSIONS: All exposures declined over time. Greatest declines in rubber dust and fumes were found in crude materials and mixing and for n-Nitrosamines in curing/vulcanising and preprocessing. This JEM and estimated LCEs will allow for evaluation of exposure-specific excess cancer risks in the British rubber industry.

Lifetime exposure to rubber dusts, fumes and N-nitrosamines and cancer mortality in a cohort of British rubber workers with 49 years follow-up.

OBJECTIVES: To quantitatively evaluate exposure-response associations between occupational exposures to rubber dust, fumes and N-nitrosamines and cancer mortality in the UK rubber industry. METHODS: Competing risk survival analyses were used to examine cancer mortality risk in a cohort of 36 441 males aged 35+ years employed in the British rubber industry in 1967, followed up to 2015 (94% mortality). Exposure measurements are based on a population-specific quantitative job-exposure matrix for rubber dust, rubber fumes and N-nitrosamines from the EU-EXASRUB project. RESULTS: Exposure (lifetime cumulative (LCE))-response associations were found for N-nitrosomorphiline and all cancers (subdistribution HR (SHR) 1.48, 95% CI 1.39 to 1.57) and cancers of the bladder, stomach, multiple myeloma, oesophagus, prostate and pancreas, as well as for N-nitrosodimethylamine and all cancers (SHR 2.08, 95% CI 1.96 to 2.21) and cancers of the bladder, stomach, leukaemia, multiple myeloma, prostate and liver. LCE to the N-nitrosamines sum were associated with increased risks from all cancers (SHR 1.89, 95% CI 1.78 to 2.01) and cancers of the lung, non-Hodgkin's lymphoma and brain. LCE to rubber dust and fumes are associated with increased mortality from all cancers (rubber dust SHR 1.67, 95% CI 1.58 to 1.78; rubber fumes SHR 1.91, 95% CI 1.80 to 2.03) and cancers of the bladder, lung, stomach, leukaemia, multiple myeloma, non-Hodgkin's lymphoma, oesophagus, prostate, pancreas and liver. CONCLUSIONS: Consistent with previous studies, N-nitrosamines exposures are associated with mortality from cancers of the bladder, lung, stomach, leukaemia, multiple myeloma, oesophagus, prostate, pancreas and liver. The long follow-up with nearly complete mortality enabled estimations of lifetime cancer mortality risk from occupational exposures in the rubber industry.

Cancer mortality in an international cohort of reinforced plastics workers exposed to styrene: a reanalysis.

OBJECTIVE: To investigate the carcinogenicity of styrene by reanalysing data from a previous international cohort study of workers in the reinforced plastics industry. METHODS: Mortality from cancers of prior interest was analysed with more detailed consideration of exposure-response relations and an updated classification of leukaemias and lymphomas in data from a previous international cohort study of 37 021 reinforced plastics workers exposed to airborne styrene. RESULTS: Increased mortality from non-Hodgkin's lymphoma (NHL) was associated with the mean level of exposure to styrene in air (relative risk (RR) 2.31, 95% CI 1.29 to 4.12 per 100 ppm), but not with cumulative styrene exposure. Similar associations with mean exposure were observed for the oesophagus (RR 2.44, 95% CI 1.11 to 5.36 per 100 ppm) and pancreas (RR 1.89, 95% CI 1.17 to 3.09). Oesophageal cancer mortality was also associated with cumulative styrene exposure lagged 20 years (RR 1.16, 95% CI 1.03 to 1.31). No other cancer, including lung cancer, was associated with any indicator of styrene exposure. CONCLUSION: This reanalysis does not substantially change the conclusions of the original study with respect to NHL or lung cancer but new evidence concerning cancers of the oesophagus and pancreas merits further investigation.

British rubber and cable industry cohort: 49-year mortality follow-up.

BACKGROUND: The International Agency for Research on Cancer (IARC) has determined there is sufficient evidence that working in the rubber manufacturing industry increases the risk of cancers of the stomach, lung, bladder and leukaemia and lymphoma. OBJECTIVES: To examine mortality patterns of a prospective cohort of men from the rubber and cable manufacturing industries in Great Britain. METHODS: SMRs were calculated for males aged 35+ years at start of follow-up in 1967-2015 using the population of England and Wales as the external comparator. Tests for homogeneity and trends in SMRs were also completed. RESULTS: For all causes, all malignant neoplasms, non-malignant respiratory diseases and circulatory diseases, SMRs were significantly elevated, and also particularly for cancers of the stomach (SMR=1.26,95% CI 1.18 to 1.36), lung (1.25,95% CI 1.21 to 1.29) and bladder (1.16,95% CI 1.05 to 1.28). However, the observed deaths for leukaemia, non-Hodgkin's lymphoma (NHL) and multiple myeloma were as expected. Bladder cancer risks were elevated only in workers exposed to antioxidants containing 1-naphthylamine and 2-naphthylamine. CONCLUSIONS: This study provides evidence of excess risks in the rubber industry for some non-cancer diseases and supports IARC's conclusions in relation to risks for cancers of the bladder, lung and stomach, but not for leukaemia, NHL or multiple myeloma.