Anne Sleeuwenhoek

Trends in wood dust inhalation exposure in the UK, 1985-2005.

OBJECTIVES Wood dust data held in the Health and Safety Executive (HSE) National Exposure DataBase (NEDB) were reviewed to investigate the long-term changes in inhalation exposure from 1985 to 2005. In addition, follow-up sampling measurements were obtained from selected companies where exposure measurements had been collected prior to 1994, thereby providing a follow-up period of at least 10 years, to determine whether changes in exposure levels had occurred, with key staff being interviewed to identify factors that might be responsible for any changes observed. METHODS Analysis of the temporal trend in exposure concentrations was performed using Linear Mixed Effect Models on the log-transformed NEDB data set and expressed as the relative annual change in concentration. RESULTS For the NEDB wood dust data, an annual decline of geometric mean (GM) exposure of 8.1% per year was found based on 1459 exposure measurements collected between 1985 and 2003. This trend was predominantly observed in data from inspection visits (measurements collected on a mandatory basis by a Specialist HSE Inspector) (n = 1009), while data from representative surveys (measurements collected on a voluntary basis to provide information on current practices and exposures) remained relatively stable. Ten follow-up surveys in individual workplaces in 2004-2005 resulted in 70 new measurements and for each of the companies resurveyed, the GM of the wood dust exposure decreased between sampling surveys. CONCLUSION Analysis of the temporal trend in UK wood dust exposure concentrations revealed declines of 8% per annum. Interviews with key long-serving employees and management suggest that factors such as technological changes in production processes, response to new legislation, and enforcement agency inspections, together with global economic trends, could be linked to the downward trends observed.

Biological monitoring of pesticide exposures in residents living near agricultural land

BackgroundThere is currently a lack of reliable information on the exposures of residents and bystanders to pesticides in the UK. Previous research has shown that the methods currently used for assessing pesticide exposure for regulatory purposes are appropriate for farm workers [1]. However, there were indications that the exposures of bystanders may sometimes be underestimated. The previous study did not collect data for residents. Therefore, this study aims to collect measurements to determine if the current methods and tools are appropriate for assessing pesticide exposure for residents living near agricultural fields.Methods/designThe study will recruit owners of farms and orchards (hereafter both will be referred to as farms) that spray their agricultural crops with certain specified pesticides, and which have residential areas in close proximity to these fields. Recruited farms will be asked to provide details of their pesticide usage throughout the spray season. Informed consenting residents (adults (18 years and over) and children(aged 4-12 years)) will be asked to provide urine samples and accompanying activity diaries during the spraying season and in additionfor a limited number of weeks before/after the spray season to allow background pesticide metabolite levels to be determined. Selected urine samples will be analysed for the pesticide metabolites of interest. Statistical analysis and mathematical modelling will use the laboratory results, along with the additional data collected from the farmers and residents, to determine systemic exposure levels amongst residents. Surveys will be carried out in selected areas of the United Kingdom over two years (2011 and 2012), covering two spraying seasons and the time between the spraying seasons.DiscussionThe described study protocol was implemented for the sample and data collection procedures carried out in 2011. Based on experience to date, no major changes to the protocol are anticipated for the 2012 spray season although the pesticides and regional areas for inclusion in 2012 are still to be confirmed.

Mortality of a cohort of workers in Great Britain with blood lead measurements

Objectives We examined the mortality of a historic cohort of workers in Great Britain with measured blood lead levels (BLLs). Methods SMRs were calculated with the population of Great Britain as the external comparator. Trends in mortality with mean and maximum BLLs and assessed lead exposure were examined using Cox regression. Results Mean follow-up length among the 9122 study participants was 29.2 years and 3466 deaths occurred. For all causes and all malignant neoplasms, the SMRs were statistically significantly raised. For disease groups of a priori interest, the SMR was significantly raised for lung cancer but not for stomach, brain, kidney, bladder or oesophageal cancers. The SMR was not increased for non-malignant kidney disease but was borderline significantly increased for circulatory diseases, for ischaemic heart disease (IHD) and cerebrovascular disease (CVD). No significant trends with exposure were observed for the cancers of interest, but for circulatory diseases and IHD, there was a statistically significant trend for increasing HR with mean and maximum BLLs. Conclusions This study found an excess of lung cancer, although the risk was not clearly associated with increasing BLLs. It also found marginally significant excesses of IHD and CVD, the former being related to mean and maximum BLLs. The finding for IHD may have been due to lead, but could also have been due to other dust exposure associated with lead exposure and possibly tobacco smoking. Further work is required to clarify this and the carcinogenicity of lead.

Occupational dermal exposure to nanoparticles and nano-enabled products: Part I—Factors affecting skin absorption

The paper reviews and critically assesses the evidence on the relevance of various skin uptake pathways for engineered nanoparticles, nano-objects, their agglomerates and aggregates (NOAA). It focuses especially in occupational settings, in the context of nanotoxicology, risk assessment, occupational medicine, medical/epidemiological surveillance efforts, and the development of relevant exposure assessment strategies. Skin uptake of nanoparticles is presented in the context of local and systemic health effects, especially contact dermatitis, skin barrier integrity, physico-chemical properties of NOAA, and predisposing risk factors, such as stratum corneum disruption due to occupational co-exposure to chemicals, and the presence of occupational skin diseases. Attention should be given to: (1) Metal NOAA, since the potential release of ions may induce local skin effects (e.g. irritation and contact dermatitis) and absorption of toxic or sensitizing metals; (2) NOAA with metal catalytic residue, since potential release of ions may also induce local skin effects and absorption of toxic metals; (3) rigid NOAA smaller than 45nm that can penetrate and permeate the skin; (4) non rigid or flexible NOAA, where due to their flexibility liposomes and micelles can penetrate and permeate the intact skin; (5) impaired skin condition of exposed workers. Furthermore, we outline possible situations where health surveillance could be appropriate where there is NOAA occupational skin exposures, e.g. when working with nanoparticles made of sensitizer metals, NOAA containing sensitizer impurities, and/or in occupations with a high prevalence of disrupted skin barrier integrity. The paper furthermore recommends a stepwise approach to evaluate risk related to NOAA to be applied in occupational exposure and risk assessment, and discusses implications related to health surveillance, labelling, and risk communication.

Cancer Risk Among Tetrafluoroethylene Synthesis and Polymerization Workers

Tetrafluoroethylene (TFE), a compound used for the production of fluorinated polymers including polytetrafluoroethylene, increases the incidence of liver and kidney cancers and leukemia in rats and mice. This is the first time the cancer risk in humans has been explored comprehensively in a cohort mortality study (1950-2008) that included all polytetrafluoroethylene production sites in Europe and North America at the time it was initiated. A job-exposure matrix (1950-2002) was developed for TFE and ammonium perfluoro-octanoate, a chemical used in the polymerization process. National reference rates were used to calculate standardized mortality ratios (SMRs) and 95% confidence intervals. Among 4,773 workers ever exposed to TFE, we found a lower rate of death from most causes, as well as increased risks for cancer of the liver (SMR = 1.27; 95% confidence interval: 0.55, 2.51; 8 deaths) and kidney (SMR = 1.44; 95% confidence interval: 0.69, 2.65; 10 deaths) and for leukemia (SMR = 1.48; 95% confidence interval: 0.77, 2.59; 12 deaths). A nonsignificant upward trend (P = 0.24) by cumulative exposure to TFE was observed for liver cancer. TFE and ammonium perfluoro-octanoate exposures were highly correlated, and therefore their separate effects could not be disentangled. This pattern of findings narrows the range of uncertainty on potential TFE carcinogenicity but cannot conclusively confirm or refute the hypothesis that TFE is carcinogenic to humans.

Occupational dermal exposure to nanoparticles and nano-enabled products: Part 2, exploration of exposure processes and methods of assessment.

Over the past decade, the primary focus of nanotoxicology and nanoenvironmental health and safety efforts has been largely on inhalation exposure to engineered nanomaterials, at the production stage, and much less on considering risks along the life cycle of nano-enabled products. Dermal exposure to nanomaterials and its health impact has been studied to a much lesser extent, and mostly in the context of intentional exposure to nano-enabled products such as in nanomedicine, cosmetics and personal care products. How concerning is dermal exposure to such nanoparticles in the context of occupational exposures? When and how should we measure it? In the first of a series of two papers (Larese Filon et al., 2016), we focused our attention on identifying conditions or situations, i.e. a combination of nanoparticle physico-chemical properties, skin barrier integrity, and occupations with high prevalence of skin disease, which deserve further investigation. This second paper focuses on the broad question of dermal exposure assessment to nanoparticles and attempts to give an overview of the mechanisms of occupational dermal exposure to nanoparticles and nano-enabled products and explores feasibility and adequacy of various methods of quantifying dermal exposure to NOAA. We provide here a conceptual framework for screening, prioritization, and assessment of dermal exposure to NOAA in occupational settings, and integrate it into a proposed framework for risk assessment.

Mortality Among Hardmetal Production Workers: Occupational Exposures

Objective: To generate quantitative exposure estimates for use in retrospective occupational cohort mortality studies of the hardmetal industry. Methods: Job-exposure matrices (JEMs) were constructed for cobalt, tungsten, and nickel over the time period 1952 to 2014. The JEMs consisted of job class categories, based on job titles and processes performed, and exposure estimates calculated from available company industrial hygiene measurements. Results: Exposure intervals of one-half order magnitude were established for all three agents. Eight job classes had significantly decreasing time trends for cobalt exposure; no significant time trends were detected for tungsten or nickel exposures. Conclusions: The levels of exposures determined for this study were similar to or lower than those previously reported for the hardmetal industry during the 1952 to 2014 study period.

Mortality Among Hardmetal Production Workers: UK Cohort and Nested Case–Control Studies

Objective: The aim of this study was to characterize the mortality at two hardmetal production factories in the United Kingdom as part of an international study. Methods: Standardized mortality ratios (SMRs) were calculated on the basis of mortality rates for England and Wales, and local rates. A nested case–control study of lung cancer was undertaken. Results: The cohort comprised 1538 workers, with tracing complete for 94.4%. All-cause mortality was statistically significantly low for all cancers and nonmalignant respiratory disease, and for lung cancer was nonsignificantly low. The SMR for lung cancer for maintenance workers was elevated, based on only six deaths. The odds ratio for lung cancer per year of exposure to hardmetal was 0.93 (0.76 to 1.13). Conclusions: In this small study, there is no evidence to support that working in the UK hardmetal manufacturing industry increased mortality from any cause including lung cancer.

Modelling exposure to pharmaceutical agents

Aerosol exposure to the active ingredients of pharmaceuticals arises in research, development and manufacturing. In most instances it is only possible to make small numbers of measurements of exposure and given the inter- and intra-individual variability it is often difficult to obtain sufficient objective data to make reliable decisions about the appropriateness of control measures. This paper describes the development and validation of an exposure model with the potential to predict airborne exposure from both new and existing operations. The model could be used to more efficiently target exposure measurement resources.

Refinement and validation of an exposure model for the pharmaceutical industry

OBJECTIVES Assessment of workers exposure is becoming increasingly critical in the pharmaceutical industry as drugs of higher potency are being manufactured. The batch nature of operations often makes it difficult to obtain sufficient numbers of exposure measurements and occupational exposure models may be useful tools in the exposure assessment process. This paper aims to describe further refinement and validation of an existing deterministic occupational exposure model to predict airborne exposure of workers in this industry. METHODS Workplace exposure assessment data (n = 381) containing all the contextual information required for the exposure model were collated from a multinational pharmaceutical company. The measured exposure levels ranged from 5 × 10⁻⁷ to 200 mg m⁻³ for largely task based samples, and included a range of handling activities, local control measures and abnormal operating conditions. Model input parameters for local control measures and handling activities were refined to reflect pharmaceutical situations. RESULTS The refined exposure model resulted in good correlations between the log-transformed model predictions and the actual measured data for the overall dataset (r(s) = 0.61, n = 381, p < 0.001) and at scenario level (r(s) = 0.69, n = 48, p < 0.001). The model overestimated scenarios with measured exposure levels < 0.1 mg m⁻³ (r(s) = 0.69, bias = 0.71, n = 46, p < 0.001), and underestimated scenarios with higher measured concentrations ( > 0.1 mg m⁻³) (r(s) = 0.59, bias = -4.9, n = 33, p < 0.001). Including information on the refined sub-parameters improved the correlations, suggesting the uncertainty in the model parameters was partly responsible for the bias. CONCLUSION Further scientific data from the pharmaceutical industry on model input parameters, particularly on the efficacy of local control measures, may help improve the accuracy of the model predictions. The refined exposure model appears to be a useful exposure assessment screening tool for the pharmaceutical industry.