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

Abstract

ObjectivesTo examine associations between occupational exposures to rubber dust, rubber fumes and N-nitrosamines and non-cancer mortality.MethodsA 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.ResultsExposure–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.ConclusionsIn 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.

Incidence of acute myocardial infarction in the workforce: Findings from the Occupational Disease Surveillance System

“… 51 However, while a small increased mortality risk was observed for ischemic and hemorrhagic stroke, no associations were detected for IHD. Further, cumulative exposure to rubber dusts, fumes and N‐nitrosamines have shown to increase the risk of IHD mortality in male rubber factory workers 52 . Seemingly, the overall lack of supporting evidence to explain some of the high, increased associations we detected for female workers across such industries, highlights an important gap in the literature.…”

Processed Meat Intake and Bladder Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cohort

“…In addition, tobacco smoke, a well-established risk factor for bladder cancer, is a main source of exogenous exposure to nitrosamines. A recent large cohort of British rubber workers with 49 years follow-up revealed that N-nitrosamines exposure was also associated with mortality from bladder cancer (19). Finally, heterocyclic amines and polycyclic aromatic hydrocarbons, which are formed by high temperature cooking, may also mediate the association between consumption of processed red meat and bladder cancer risk (20,21).…”

Ameliorative Effects of Aspergillus awamori against the Initiation of Hepatocarcinogenesis Induced by Diethylnitrosamine in a Rat Model: Regulation of Cyp19 and p53 Gene Expression

“…Hepatitis viral infection, alcohol, aflatoxins, environmental and industrial pollutants, and air and water contamination are the most common factors linked with liver cancer [4]. Diethylnitrosamine (DEN) is a wellknown hepatocarcinogenic agent found in cigarette smoke, water, cured and fried foods, cheese from cheddars, chemicals from the farming industry, cosmetics, and pharmaceutical products [5,6]. By inhibiting several enzymes involved in the DNA repair process, DEN causes liver cancer in the experimental animal model [7,8] in addition to activation of cytochrome P450 enzymes, forming reactive electrophile enzymes that cause oxidation stress, which contributes to cytotoxicity, mutagens and cancers [9].…”