Longitudinal changes in cardiovascular disease-related proteins in welders.

OBJECTIVE: Occupational exposure to welding fumes is linked to a higher risk of cardiovascular disease; however, the threshold exposure level is unknown. Here, we aimed to identify changes in proteins associated with cardiovascular disease in relation to exposure to welding fumes. METHODS: Data were obtained from two timepoints six years apart for 338 non-smoking men (171 welders, 167 controls); of these, 174 (78 welders, 96 controls) had measurements available at both timepoints. Exposure was measured as personal respirable dust (adjusted for personal protective equipment), welding years, and cumulative exposure. Proximity extension assays were used to measure a panel of 92 proteins involved in cardiovascular processes in serum samples. Linear mixed models were used for longitudinal analysis. The biological functions and diseases related to the identified proteins were explored using the Ingenuity Pathway Analysis software. RESULTS: At both timepoints, the median respirable dust exposure was 0.7 mg/m3 for the welders. Seven proteins were differentially abundant between the welders and controls and increased incrementally with respirable dust: FGF23, CEACAM8, CD40L, PGF, CXCL1, CD84, and HO1. CD84 was significant after adjusting for multiple comparisons. These proteins have been linked to disorders of blood pressure, damage related to clogged blood vessels, and chronic inflammatory disorders. CONCLUSION: Exposure to mild steel welding fumes below current occupational exposure limits for respirable particles and welding fumes in Europe and the US (1-5 mg/m3) was associated with changes in the abundance of proteins related to cardiovascular disease. Further research should evaluate the utility of these proteins as prospective biomarkers of occupational cardiovascular disease.

[Comparison and analysis research on occupational exposure limits of coal dust between China and foreign countries].

Objective: To study and compare the occupational exposure limits (OELs) of coal dust between China and foreign countries, understand the OEL of coal dust in China, and provide data and basis for revising the OEL of coal dust in China. Methods: In August 2023, by searching the official websites of limits setting institutions in relevant countries and regions at home and abroad, collecting and sorting out the OELs of coal dust issued by 10 limit setting institutions in 6 countries and the background information of the formulation, and conducting specific analysis on the classification, limit level and formulation principles of coal dust OEL in each country/institution. Results: In China and Japan, the total dust and respirable dust of coal dust OEL were established respectively, while in other countries, only the time-weighted average concentration (TWA) of respirable coal dust exposure was established. The TWA prescribed by China's Notional Health Commission, the United States Occupational Safety and Health Administration (OSHA) , the United States Mining Safety and Health Administration (MSHA) and the Australian Safety Work Bureau when the SiO(2) content was less than 5% were 5, 2.4, 2 and 3 mg/m(3) respectively. China GBZ 2.1-2019 sets the limit of 2.5 mg/m(3) for respirable coal dust with SiO(2) content less than 10%. The TWA set by the American Conference of Government Industrial Hygienists (ACGIH) and the South African Department of Mines and Energy (DME) for anthracite coal were 0.4 and 0.8 mg/m(3), respectively, and bituminous coal or lignite were 0.9 and 1.8 mg/m(3), respectively. The respirable coal dust TWA set by the National Institute for Occupational Safety and Health (NIOSH) in the United States was 1 mg/m(3), and the TWA set by the New Zealand Work Safety Authority was 3 mg/m(3). Conclusion: At present, the OEL of coal dust in China is at a relatively loose level, and it is suggested to further explore the possibility of revising coal dust OEL.

Relationship between exposure to metalworking fluids and nonalcoholic fatty liver disease.

OBJECTIVE: The relationship between metalworking fluids (MWFs) and nonalcoholic fatty liver disease (NAFLD) has not been previously explored. We aim to investigate the relationship between occupational exposure to MWFs and the prevalence of NAFLD and to determine the cumulative exposure threshold per day. METHODS: In 2020, 2079 employees were selected randomly from one computer numerical control machining factory in Wuxi for a questionnaire survey, and occupational health examinations were conducted at the affiliated branch of Wuxi Eighth People's Hospital. MWF samples were collected within the factory using the National Institute for Occupational Safety and Health (NIOSH) 5524 method. NAFLD was defined as having a hepatic steatosis index (HSI) ≥ 36 without significant alcohol consumption. The relationship between NAFLD and MWFs was analyzed using logistic regression, and the daily exposure threshold was calculated using R software. RESULTS: MWF exposure was found to be a risk factor for NAFLD in exposed workers compared to the non-exposed group. The OR for NAFLD in workers exposed to MWFs compared to controls was 1.42 (95% CI: 1.04-1.95). An increased risk of NAFLD was shown to be associated with an increasing dose. The daily exposure dose threshold to MWFs was found to be 6.54 mg/m3 (OR = 2.09, 95% CI: 1.24-3.52). CONCLUSION: An association between occupational exposure to MWFs and NAFLD was found. As the concentration of exposure rose, the prevalence of NAFLD was also escalated.

Club cell protein (CC16) in serum as an effect marker for small airway epithelial damage caused by diesel exhaust and blasting fumes in potash mining.

OBJECTIVE: The effect marker club cell protein (CC16) is secreted by the epithelium of the small respiratory tract into its lumen and passes into the blood. Increased amounts of CC16 in serum are observed during acute epithelial lung injury due to air pollutants. CC16 in serum was determined as part of this cross-sectional study in underground potash miners on acute and chronic health effects from exposures to diesel exhaust and blasting fumes. METHODS: Nitrogen oxides, carbon monoxide, and diesel particulate matter were measured in 672 workers at a German potash mining site on a person-by-person basis over an early shift or midday shift, together with CC16 serum concentrations before and after the respective shift. CC16 concentrations and CC16 shift-differences were evaluated with respect to personal exposure measurements and other quantitative variables by Spearman rank correlation coefficients. CC16 shift-differences were modeled using multiple linear regression. Above-ground workers as reference group were compared to the exposed underground workers. RESULTS: Serum concentrations of CC16 were influenced by personal characteristics such as age, smoking status, and renal function. Moreover, they showed a circadian rhythm. While no statistically significant effects of work-related exposure on CC16 concentrations were seen in never smokers, such effects were evident in current smokers. CONCLUSION: The small airways of current smokers appeared to be vulnerable to the combination of measured work-related exposures and individual exposure to smoking. Therefore, as health protection of smokers exposed to diesel exhaust and blasting fumes, smoking cessation is strongly recommended.

[Research progress on health hazards of oil mist].

Metal working fluidis widely used as coolant, lubricant and rust remover in mechanical processing. Oil mist will be formed in the process of metal working fluid. The composition of oil mist is complex, which can produce many adverse effects on the environment and operators. This paper reviews the health hazards of metal working fluid oil mist on human skin, respiratory system, teratogenic and carcinogenic aspects, and discusses the establishment of occupational exposure limits in workplaces of oil mist in foreign countries, in order to provide reference for the prevention and control of occupational health risks of metal working fluid oil mist and the establishment of occupational exposure limits of oil mist in workplaces in China.

[Study on the occupational exposure limit of glyphosate in the air of workplace].

Objective: To establish occupational exposure limits for glyphosate in workplace air. Methods: In November 2014, by searching the documents of the United States Environmental Protection Agency (EPA) on glyphosate toxicity, the toxicity data and clinical symptoms of glyphosate toxicity were collected through various literature databases, and the target organs of glyphosate toxicity were determined. A total of 5 representative production enterprises in Jiangsu Province and Shandong Province were selected for field investigation. A total of 968 people were selected as the study subjects, including 526 workers exposed to glyphosate as the contact group, and 442 off-site (such as financial, administrative, etc.) workers with enterprises as the control group. Health examination was carried out in the exposure group and the control group to observe the damage of target organs of workers with different exposure concentrations and determine the occupational exposure limit. Results: The main target organs of glyphosate are liver and kidney and its effect on cholinesterase activity. The time-weighted average concentration (TWA) of glyphosate exposure in the exposure group was <0.03~48.91 mg/m(3), and there were statistically significant differences in liver and renal function between the exposure group and the control group (P<0.05). When the concentration of glyphosate in the air was higher than 5 mg/m3, there was a statistically significant difference in the abnormal rate of renal function between the exposure group and the control group (P<0.05) . Conclusion: The study sets the occupational exposure limit of glyphosate as 5 mg/m(3). The safety of this standard conforms to the relevant requirements of toxicology and occupational disease epidemiology, and also conforms to the existing economic and technological level in my country, and is highly feasible.

Core temperature and heart rate at the upper limit of the prescriptive zone.

The expressed goal of limiting workplace heat stress exposures to a core temperature (Tc ) of 38°C traces back to a 1969 World Health Organization Technical Report (WHO Series 412). The actual goal was to limit exposures to the upper limit of the prescriptive zone (ULPZ). To explore the physiological strain at the ULPZ, progressive heat stress protocol data from Penn State University (PSU) and University of South Florida (USF) below and at the ULPZ were used to articulate the relation of Tc and heart rate (HR) to metabolic rate (MR) with consideration of acclimatization state, clothing, exposure condition (PreULPZ vs. ULPZ), and sex. Regression models demonstrated the association of MR and sex with Tc and HR. At the ULPZ, women had systematically higher values of Tc and HR than men at the same MR likely due to higher relative demands. There was no effect for acclimatization state and clothing. As expected for individuals, Tc was practically constant below the ULPZ and HR exhibited increasing values approaching the ULPZ. At 490 W, the high MR cited in the WHO document, the mean Tc for men was near the 38°C limit with systematically lower Tc at lower MRs.

Systemic inflammatory effects of zinc oxide particles: is a re-evaluation of exposure limits needed?

Exposure to airborne substances such as gases, vapours, and particles remains a relevant health risk in many workplaces. A current topic and cause for discussion is the investigation of the health effects of particles containing zinc oxide (ZnO). Among other data, those collected from our study on human exposure data of ZnO in 2018 prompted the National Research Centre for the Working Environment 2021 to formulate a new, sharply lowered proposed occupational exposure limit (OEL) for zinc in workplaces. Since the publication of the Danish report, further studies have been conducted with ZnO. In the following text, all arguments for deriving this new limit value for zinc from the report are discussed, extended with the more recent data since 2018. It should be noted that especially the application of time extrapolation factors needs further discussion and harmonization between regulatory authorities. From our point of view, the data situation can justify a higher OEL for zinc than that proposed by the Danish National Research Centre for the Working Environment.

Distribution of upper limit of the prescriptive zone values for acclimatized and unacclimatized individuals.

Heat stress has an adverse impact on worker health and well-being, and the effects will increase with more frequent and severe heat events associated with global warming. Acclimatization to heat stress is widely considered to be a critical mitigation strategy and wet bulb globe temperature- (WBGT-) based occupational standards and guidelines contain adjustments for acclimatization. The purpose here was to 1) compare the mean values for the upper limit of the prescriptive zone (ULPZ, below which the rise in core temperature is minimal) between unacclimatized and acclimatized men and women; 2) demonstrate that the change in the occupational exposure limit (ΔOEL) due to acclimatization is independent of metabolic rate; 3) examine the relation between ΔOEL and body surface area (BSA); and 4) compare the exposure-response curves between unacclimatized and acclimatized populations. Empirically derived ULPZ data for unacclimatized participants from Pennsylvania State University (PSU) and acclimatized participants from University of South Florida (USF) were used to explore the difference between unacclimatized and acclimatized heat exposure limits. The findings provide support for a constant 3°C WBGT OEL decrease to account for unacclimatized workers. Body surface area explained part of the difference in ULPZ values between men and women. In addition, the pooled PSU and USF data provide insight into the distribution of individual values for the ULPZ among young, healthy unacclimatized and acclimatized populations in support of occupational heat stress guidelines.NEW & NOTEWORTHY Occupational exposure limit guidelines using wet bulb globe temperature (WBGT) distinguish between acclimatized and unacclimatized workers with about a 3°C difference between them. For the first time, empirical data from two laboratories provide support for acclimatization state adjustments. Using a constant difference rather than increasing differences with metabolic rate better describes the limit for unacclimatized participants. Furthermore, the lower upper limit of the prescriptive zone (ULPZ) values set forth for women do not relate to fitness level but are partly explained by their smaller body surface area (BSA). An examination of individual ULPZ values suggests that many unacclimatized individuals should be able to sustain safe work at the exposure limit for acclimatized workers.

Approaches for the setting of occupational exposure limits (OELs) for carcinogens.

This article addresses issues of importance for occupational exposure limits (OELs) and chemical carcinogens with a focus on non-threshold carcinogens. It comprises scientific as well as regulatory issues. It is an overview, not a comprehensive review. A central topic is mechanistic research and insights, and its implications for cancer risk assessment. Alongside scientific advancements, the approaches of hazard identification and qualitative and quantitative risk assessment have developed over the years. The key steps in a quantitative risk assessment are outlined, with special attention given to the dose-response assessment and the derivation of an OEL using risk calculations or default assessment factors. The work procedures of several bodies performing cancer hazard identifications and quantitative risk assessments, as well as regulatory procedures to derive OELs for non-threshold carcinogens, are presented. Non-threshold carcinogens for which the European Union (EU) introduced binding OELs in 2017-2019 serve as illustrations together with some currently used strategies in the EU and elsewhere. Available knowledge supports the derivation of health-based OELs (Hb-OELs) for non-threshold carcinogens, and the use of a risk-based approach with low-dose linear extrapolation (linear non-threshold, LNT) as the default for non-threshold carcinogens. However, there is a need to develop methods that allow recent years' advances in cancer research to be used for improving risk estimates. It is recommended that defined risk levels (terminology and numerical values) are harmonised, and that both collective and individual risks are considered and clearly communicated. Socioeconomic aspects should be dealt with transparently and separated from the scientific health risk assessment.

Impact of diesel exhaust exposure on urinary 1-hydroxypyrene in underground salt and potash workers.

BACKGROUND: Diesel engine exhaust (DEE) and some of the polycyclic aromatic hydrocarbons (PAH) it contains are carcinogenic to humans (for example benzo(a)pyrene) and can cause lung cancer in workers. The objective of this study was to assess exposures to DEE and its component PAH and the potential associations between these two health hazards in a salt and potash mining population. METHODS: Between 2017 and 2019, 1003 underground workers (mining n = 801, maintenance n = 202) and 243 above-ground facility workers from two German mines participated. Personal exposure to DEE was assessed in air as elemental carbon for diesel particulate matter (EC-DPM), whereas exposure to PAH was assessed in pre- and post-shift urine samples in terms of 1-hydroxypyrene (1-OHP). Associations between EC-DPM and 1-OHP were studied using linear regression models. RESULTS: The highest EC-DPM exposures were measured in mining workers (median 0.06 mg/m³) followed by workers in the maintenance (0.03 mg/m3) and facility areas (<0.02 mg/m3). Exposures above the current German occupational threshold level of 0.05 mg/m3 were observed in 56%, 17%, and 5% of mining, maintenance and facility workers, respectively. 1-OHP increased statistically significantly across a work shift in underground workers but not in facility workers. Regression analyses revealed an increase of post-shift 1-OHP by almost 80% in mining and 40% in maintenance compared with facility workers. 1-OHP increased with increasing EC-DPM among underground workers. However, internal exposure of 1-OHP mainly remained at levels similar to those of the German general population in more than 90% of the urine samples. CONCLUSIONS: While exposures to DEE above the current German OEL for EC-DPM are quite common in the studied population of underground salt and potash miners (39.5% overall), urinary concentrations of 1-OHP did not reflect these findings.

The chemicals between us-First results of the cluster analyses on anatomy embalming procedures in the German-speaking countries.

Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe. Clusters were established for "ethanol"-, formaldehyde-based ("FA"), and "other" embalming procedures, depending on the chemicals considered the most relevant for each protocol. The logistical framework, volumes of chemicals, and infrastructure were found to be highly diverse between the groups and protocols. Formaldehyde quantities deployed per annum were three-fold higher in the "FA" (223 L/a) compared to the "ethanol" (71.0 L/a) group, but not for "other" (97.8 L/a), though the volumes injected per body were similar. "FA" was strongly related to table-borne air ventilation and total fixative volumes ≤1000 L. "Ethanol" was strongly related to total fixative volumes >1000 L, ceiling- and floor-borne air ventilation, and explosion-proof facilities. Air ventilation was found to be installed symmetrically in the mortuary and dissection facilities. Certain predictors exist for the interplay between the embalming used in a given infrastructure and technical measures. The here-established cluster analysis may serve as decision supportive tool when considering altering embalming protocols or establishing joint protocols between institutions, following a best practice approach to cater toward best-suited tissue characteristics for educational purposes, while simultaneously addressing future demands on exposure limits.

Contribution of toxicological pathology to occupational health: lung carcinogenicity of fibrous and particulate substances in rats.

In this review, we focus on the rat pulmonary carcinogenicity of two solid substances, fibrous multi-walled carbon nanotube (MWCNT) and particulate indium tin oxide (ITO). Inhalation exposure to MWNT-7, a type of MWCNTs, and ITO induced lung carcinogenicity in both male and female rats. Toxicity to the alveolar epithelium is induced by macrophages undergoing frustrated phagocytosis or frustrated degradation of engulfed particles (referred to as frustrated macrophages). Melted macrophage contents contribute significantly to development of hyperplasia of the alveolar epithelium, which eventually results in the induction of lung carcinoma. MWNT-7 and ITO induce secondary genotoxicity; consequently, a no-observed-adverse-effect level can be applied to these materials rather than benchmark doses that are used for non-threshold carcinogens. Thus, establishing occupational exposure limit values for MWNT-7 and ITO based on the existence of a carcinogenic threshold is reasonable.

Use of the benchmark-dose (BMD) approach to derive occupational exposure limits (OELs) for genotoxic carcinogens: N-nitrosamines.

N-Nitrosamines are potent carcinogens and considered non-threshold carcinogens in various regulatory domains. However, recent data indicate the existence of a threshold for genotoxicity, which can be adequately demonstrated. This aspect has a critical impact on selecting the methodology that is applied to derive occupational exposure limits (OELs). OELs are used to protect workers potentially exposed to various chemicals by supporting the selection of appropriate control measures and ultimately reducing the risk of occupational cancer. Occupational exposures to nitrosamines occur during manufacturing processes, mainly in the rubber and chemical industry. The present study derives OELs for inhaled N-nitrosamines, employing the benchmark dose (BMD) approach if data are adequate and read-across for nitrosamines without adequate data. Additionally, benchmark dose lower confidence limit (BMDL) is preferred and more suitable point-of-departure (PoD) to calculate human health guidance values, including OEL. The lowest OEL (0.2 µg/m3 ) was derived for nitrosodiethylamine (NDEA), and nitrosopiperidine (NPIP) (OEL = 0.2 µg/m3 ), followed by nitrosopyrrolidine (NPYR) (0.4 µg/m3 ), nitrosodimethylamine (NDMA), nitrosodimethylamine (NMEA), and nitrosodipropylamine (NDPA) (0.5 µg/m3 ), nitrosomorpholine (NMOR) (OEL = 1 µg/m3 ), and nitrosodibutylamine (NDBA) (OEL = 2.5 µg/m3 ). Limits based on "non-threshold" TD50 slope calculation were within a 10-fold range. These proposed OELs do not consider skin absorption of nitrosamines, which is also a possible route of entry into the body, nor oral or other environmental sources. Furthermore, we recommend setting a limit for total nitrosamines based on the occupational exposure scenario and potency of components.

A cohort study of wastewater treatment plant workers: Association between levels of biomarkers of systemic inflammation and exposure to bacteria and fungi, and endotoxin as measured using two methods.

Work in wastewater treatment plants (WWTPs) can be associated with exposure to airborne microorganisms and endotoxin from the working environment. The aim of this study was to obtain knowledge about whether serum levels of the markers of systemic inflammation, C-reactive protein (CRP) and serum amyloid A (SAA), are associated with personal exposure to endotoxin, measured using the Limulus (endotoxinLimulus) and the rFC (endotoxinrFC) assays, as well as bacteria and fungi in a cohort of WWTP workers. Exposure and blood samples were collected for 11 workers over one year. Exposure to endotoxinLimulus-day and endotoxinrFC-day correlated significantly (r = 0.80, p<0.0001, n = 104), but endotoxinLimulus-day was 4.4 (Geometric mean (GM) value) times higher than endotoxinrFC-day (p<0.0001). The endotoxinLimulus-day, endotoxinrFC-day, bacteria, and fungal exposure as well as serum levels of CRP-day (GM=1.4 mg/l) and SAA-day (GM=12 mg/l) differed between workers. Serum levels of SAAday correlated significantly with CRPday (r = 0.30, p = 0.0068). The serum levels of CRPday were associated significantly with exposure to endotoxinLimulus-day. Exposure, SAA and CRP data were also analyzed as av. of each season, and SAAseason was associated positively and significantly with endotoxinLimulus-season and endotoxinrFC-season and negatively with fungalseason exposure. In conclusion, CRPday was associated with the endotoxinLimulus-day and SAAseason with endotoxinLimulus-season and endotoxinrFC-season exposure. Thus, we hereby document that WWTP workers are exposed to airborne endotoxin which seems to have a negative impact on their health.

Uranium: an overview of physicochemical properties, exposure assessment methodologies, and health effects of environmental and occupational exposure.

Uranium is chemo- and radiotoxic element which can cause multifactorial health hazards. Natural and anthropogenic uranium contamination raises concerns about potential public health problems. Natural contamination plays a significant role with regard to uranium exposure in the general population, whereas anthropogenic contamination leads to occupational uranium exposure, particularly in nuclear industry workers. In this review, we present a state-of-the-art status concerning uranium-induced health risks with a focus on epidemiological findings of uranium processing and enrichment plant workers. We provide a general overview of physicochemical properties of uranium and analytical methods for measuring or monitoring uranium, describe environmental and occupational exposure scenarios, and discuss the challenges for objectively investigating risks from uranium exposure.

The HBM4EU chromates study - Outcomes and impacts on EU policies and occupational health practices.

Within the EU human biomonitoring initiative (HBM4EU), a targeted, multi-national study on occupational exposure to hexavalent chromium (Cr(VI)) was performed. Cr(VI) is currently regulated in EU under REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) and under occupational safety and health (OSH) legislation. It has recently been subject to regulatory actions to improve its risk management in European workplaces. Analysis of the data obtained within the HBM4EU chromates study provides support both for the implementation of these regulatory actions and for national enforcement programs and may also contribute to the updating of occupational limit values (OELs) and biological limit values for Cr(VI). It also provides useful insights on the contribution of different risk management measures (RMMs) to further reduce the exposure to Cr(VI) and may support the evaluation of applications for authorisation under REACH. Findings on chrome platers' additional per- and polyfluoroalkyl substances (PFAS) exposure highlight the need to also pay attention to this substance group in the metals sector. A survey performed to evaluate the policy relevance of the HBM4EU chromates study findings supports the usefulness of the study results. According to the responses received from the survey, the HBM4EU chromates study was able to demonstrate the added value of the human biomonitoring (HBM) approach in assessment and management of occupational exposure to Cr(VI). For future occupational studies, we emphasise the need for engagement of policy makers and regulators throughout the whole research process to ensure awareness, relevance and uptake of the results in future policies.

The utility of hERG channel inhibition data in the derivation of occupational exposure limits.

Inhibition of the human ether-à-go-go (hERG) channel may lead to QT prolongation and fatal arrhythmia. While pharmaceutical drug candidates that exhibit potent hERG channel inhibition often fail early in development, many drugs with both cardiac and non-cardiac indications proceed to market. In this study, the relationship between in vitro hERG channel inhibition and published occupational exposure limit (OEL) was evaluated. A total of 23 cardiac drugs and 44 drugs with non-cardiac indications with published hERG channel IC50 and published OELs were identified. There was an apparent relationship between hERG IC50 potency and the OEL for cardiac and non-cardiac drugs. Twenty cardiac and non-cardiac drugs were identified that had a potent hERG IC50 (≤25 µM) and a contrastingly large OEL value (≥100 µg/m3). OELs or hazard banding corresponding to ≤100 µg/m3 should be sufficiently protective of effects following occupational exposure to the majority of APIs with hERG IC50 values ≤ 100 µM. It is important to consider hERG IC50 values and possible cardiac effects when deriving OEL values for drugs, regardless of indication. These considerations may be particularly important early in the drug development process for establishing exposure control bands for drugs that do not yet have full clinical safety data.

Towards health-based nano reference values (HNRVs) for occupational exposure: Recommendations from an expert panel.

Unique physicochemical characteristics of engineered nanomaterials (ENMs) suggest the need for nanomaterial-specific occupational exposure limits (OELs). Setting these limits remains a challenge. Therefore, the aim of this study was to set out a framework to evaluate the feasibility of deriving advisory health-based occupational limit values for groups of ENMs, based on scientific knowledge. We have used an expert panel approach to address three questions: 1) What ENM-categories should be distinguished to derive advisory health-based occupational limit values (or health-based Nano Reference Values, HNRVs) for groups of ENMs? 2) What evidence would be needed to define values for these categories? And 3) How much effort would it take to achieve this? The panel experts distinguished six possible categories of HNRVs: A) WHO-fiber-like high aspect ratio ENMs (HARNs), B) Non-WHO-fiber-like HARNs and other non-spheroidal ENMs, C) readily soluble spheroidal ENMs, D) biopersistent spheroidal ENMs with unknown toxicity, E) biopersistent spheroidal ENMs with substance-specific toxicity and F) biopersistent spheroidal ENMs with relatively low substance-specific toxicity. For category A, the WHO-fiber-like HARNs, agreement was reached on criteria defining this category and the approach of using health-based risk estimates for asbestos to derive the HNRV. For category B, a quite heterogeneous category, more toxicity data are needed to set an HNRV. For category C, readily soluble spheroidal ENMs, using the OEL of their molecular or ionic counterpart would be a good starting point. For the biopersistent ENMs with unknown toxicity, HNRVs cannot be applied as case-by-case testing is required. For the other biopersistent ENMs in category E and F, we make several recommendations that can facilitate the derivation of these HNRVs. The proposed categories and recommendations as outlined by this expert panel can serve as a reference point for derivation of HNRVs when health-based OELs for ENMs are not yet available.

Underground salt and potash workers exposed to nitrogen oxides and diesel exhaust: assessment of specific effect biomarkers.

PURPOSE: Occupational exposure limits (OEL) for nitrogen oxides (NO, NO2) and diesel exhaust (EC-DPM) were reassessed by the German authorities in 2016/2017. We performed a clinical cross-sectional study among salt and potash underground workers exposed to these substances at relatively high levels to examine possible indicators of acute effects on workers' health. METHODS: We measured post- versus pre-shift differences in cardiovascular, inflammatory, immune, and respiratory effect biomarkers and assessed their associations with personal exposures measured during the same shift. We also compared post- versus pre-shift differences in biomarker levels between exposure groups defined based on work site and job type. RESULTS: None of the above-ground workers exceeded the OEL for NO2 and only 5% exceeded the OEL for EC-DPM exposure. Among underground workers, 33% of miners and 7% underground maintenance workers exceeded the OEL for NO2; the OEL for EC-DPM was exceeded by 56% of miners and 17% of maintenance workers. Some effect biomarkers (thrombocytes, neutrophils, MPO, TNF-α, IgE, FeNO) showed statistically significant differences between pre- versus post-shift measurements; however, there were no consistent associations between pre- and post-shift differences and exposure group or personal exposure measurements during the shift. CONCLUSIONS: We did not find evidence of associations between workplace exposure to NO, NO2 or EC-DPM and clinically relevant indicators of acute cardiovascular, inflammatory and immune, or respiratory effects among salt and potash underground workers in Germany.