Associations of Occupational Styrene Exposure With Risk of Encephalopathy and Unspecified Dementia: A Long-Term Follow-up Study of Workers in the Reinforced Plastics Industry

Exposure to industrial solvents has been associated with encephalopathy. Styrene is a neurotoxic industrial solvent, and we investigated the long-term risk of encephalopathy and unspecified dementia following styrene exposure. We followed 72,465 workers in the reinforced plastics industry in Denmark (1977–2011) and identified incident cases of encephalopathy (n = 228) and unspecified dementia (n = 565) in national registers. Individual styrene exposure levels were modeled from information on occupation, measurements of work place styrene levels, product, process, and years of employment. Adjusted analyses were performed using a discrete survival function. A positive trend for encephalopathy (P < 0.01) and a negative trend for unspecified dementia (P = 0.03) were seen with cumulative styrene exposure accrued during the recent period of up to 15 years. For unspecified dementia and the combination of unspecified dementia and encephalopathy, a positive trend was indicated when applying a 30-year exposure lag (P = 0.13 and P = 0.07). The risk patterns seen following recent exposure probably reflect diagnostic criteria for encephalopathy requiring recent industrial solvent exposure and referral bias rather than association with styrene exposure, while the increasing risk observed for unspecified dementia and the combination of encephalopathy and unspecified dementia following distant exposure indicates an increased risk of dementia following styrene exposure with a long latency period.

Exposure–response assessment of cancer mortality in styrene-exposed boatbuilders

ObjectivesTo improve exposure estimates and reexamine exposure–response relationships between cumulative styrene exposure and cancer mortality in a previously studied cohort of US boatbuilders exposed between 1959 and 1978 and followed through 2016.MethodsCumulative styrene exposure was estimated from work assignments and air-sampling data. Exposure–response relationships between styrene and select cancers were examined in Cox proportional hazards models matched on attained age, sex, race, birth cohort and employment duration. Models adjusted for socioeconomic status (SES). Exposures were lagged 10 years or by a period maximising the likelihood. HRs included 95% profile-likelihood CIs. Actuarial methods were used to estimate the styrene exposure corresponding to 10-4 extra lifetime risk.ResultsThe cohort (n= 5163) contributed 201 951 person-years. Exposures were right-skewed, with mean and median of 31 and 5.7 ppm-years, respectively. Positive, monotonic exposure–response associations were evident for leukaemia (HR at 50 ppm-years styrene = 1.46; 95% CI 1.04 to 1.97) and bladder cancer (HR at 50 ppm-years styrene =1.64; 95% CI 1.14 to 2.33). There was no evidence of confounding by SES. A working lifetime exposure to 0.05 ppm styrene corresponded to one extra leukaemia death per 10 000 workers.ConclusionsThe study contributes evidence of exposure–response associations between cumulative styrene exposure and cancer. Simple risk projections at current exposure levels indicate a need for formal risk assessment. Future recommendations on worker protection would benefit from additional research clarifying cancer risks from styrene exposure.

A follow-up study of occupational styrene exposure and risk of autoimmune rheumatic diseases

ObjectivesIncreased risk has been suggested for autoimmune rheumatic diseases following solvent exposure. The evidence for specific solvents is limited, and little is known about exposure–response relations. Styrene is an aromatic, organic solvent and the objective of this study was to analyse the association between occupational styrene exposure and autoimmune rheumatic diseases in men and women.MethodsWe followed 72 212 styrene-exposed workers of the Danish reinforced plastics industry from 1979 to 2012. We modelled full work history of styrene exposure from employment history, survey data and historical styrene exposure measurements. We identified cases in the national patient registry and investigated gender-specific exposure–response relations by cumulative styrene exposure for different exposure time windows adjusting for age, calendar year and educational level.ResultsDuring 1 515 126 person-years of follow-up, we identified 718 cases of an autoimmune rheumatic disease, of which 73% were rheumatoid arthritis. When adjusting for potential confounders and comparing the highest with the lowest styrene exposure tertile, we observed a statistically non-significantly increased risk of systemic sclerosis among women (incidence rate ratio (IRR)=2.50; 95% CI 0.50 to 12.50) and men (IRR=1.86; 95 % CI 0.50 to 7.00), based on 9 and 22 cases, respectively. Results were inconsistent for the other autoimmune rheumatic diseases examined.ConclusionThis study suggests an association between occupational styrene exposure and systemic sclerosis in men as well as in women but based on few cases. This is a new finding and has to be replicated before conclusions can be drawn.

O2D.1 A follow-up study of occupational styrene exposure and risk of systemic sclerosis, rheumatoid arthritis, and other systemic autoimmune rheumatological diseases

BackgroundIncreased risk of systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, primary systemic vasculitis, and systemic Sjogren’s syndrome has been suggested following occupational solvent exposure. The evidence for specific solvents is, however, limited and little is known about exposure and risk patterns.AimOur aim is to examine the exposure response relation for systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, primary systemic vasculitis, and systemic Sjogren’s syndrome following occupational styrene exposure.MethodsWe followed 72 467 styrene exposed workers of the Danish reinforced plastics industry from 1977–2012. We modelled styrene exposure from employment history, survey data and historical styrene exposure measurements. We identified cases in a national patient register, and investigated gender specific exposure response relations by cumulative styrene exposure for different exposure time windows adjusting for age, decade, educational level and a proxy for tobacco smoking.ResultsDuring 1,553,577 person-years, we identified 223 women and 453 men diagnosed with a systemic autoimmune rheumatological disease, of which three out of four were rheumatoid arthritis. When adjusting for potential confounders and comparing the highest with the lowest styrene exposure tertile, we observed a statistically non- significantly increased risk of systemic sclerosis among men (IRR=1.79; 95% CI 0.48–6.87) and women (IRR=2.58; 95% CI 0.51–12.94), based on 20 and 9 cases respectively. However, for women with systemic sclerosis, we saw a significantly increasing trend of 1.19 (1.01–1.40) pr. 100 mg/m3-years. Increased risks were also suggested for primary systemic vasculitis (IRR=2.32; 95% CI 0.63–8.52) and rheumatoid arthritis (IRR=1.26; 95% CI 0.95–1.67) among men. Analyses of exposure time windows suggest a latency period for rheumatoid arthritis of about 15 years.ConclusionThis study might indicate that styrene exposure is associated with the occurrence of systemic sclerosis among men and women, and primary systemic vasculitis and rheumatoid arthritis among men.

O5B.2 Dermal exposure to solvents: a need for quantitative analysis

For many years, airborne exposure was considered as the main work-related exposure and efforts have been made both on air monitoring and reduction of respiratory exposure. Nevertheless, recent studies have shown that preventive strategies with an exclusive focus on airborne exposures may falsely indicate a ‘safe’ environment. In 2014, WHO highlighted the importance of dermal exposure and its potential impact on human health. Moreover, it stipulated that the current technical and knowledge gaps related to the assessment of skin exposure have major lacunae.In this context, there is an increased demand for standardized methods and tools for measuring and assessing skin exposure to hazardous agents.We have developed an analytical method to simultaneously identify and quantify 195 volatile organic compounds (VOC) in dermal patches with activated charcoal cloth (ACC). Furthermore, we have done several field studies in different industrial settings, by the simultaneous assessment of dermal exposure using the ACC patches (on the hand, arm and neck), together with assessment of the respiratory exposure and determining the actual internal dose via urinary biomonitoring. Toluene, acetone and styrene exposure was found in a thermoplastic panel factory, styrene exposure in a composites body parts manufacturer, limonene and 1-methoxy-2-propanol exposure in a company that produces and prints plastic cartridges, and acetone and toluene in a pharmaceutical company. The results obtained from the quantitative ACC patches have been compared to the data obtained using Riskofderm for skin exposure, and the penetration through the skin was further estimated using IH-Skinperm and correlated with biomonitoring results.Based on the analytical development and the results of the different field studies, we can conclude that ACC patches represent a suitable technique to evaluate the deposition of VOCs on the skin. We further believe that assessing dermal exposure to solvents using ACC patches can substantially improve occupational health programs.