Using Evidence Integration Techniques in the Development of Health-Based Occupational Exposure Levels.

Development of toxicology-based criteria such as occupational exposure levels (OELs) are rarely straightforward. This process requires a rigorous review of the literature, searching for patterns in toxicity, biological plausibility, coherence, and dose-response relationships. Despite the direct applicability, human data are rarely used primarily because of imprecise exposure estimates, unknown influence of assumptions, and confounding factors. As a result, high reliance is often placed on laboratory animal data. Often, data from a single study is typically used to represent an entire database to extrapolate an OEL, even for data-rich compounds. Here we present a holistic framework for evaluating epidemiological, controlled in vivo, mechanistic/in vitro, and computational evidence that can be useful in deriving OELs. It begins with describing a documented review process of the literature, followed by sorting of data into either controlled laboratory in vivo, in silico/read-across, mechanistic/in vitro, or epidemiological/field data categories. Studies are then evaluated and qualified based on rigor, risk of bias, and applicability for point of departure development. Other data (eg, in vitro, in silico estimates, read-across data and mechanistic information, and data that failed to meet the former criteria) are used alongside qualified epidemiological exposure estimates to help inform points of departure or human-equivalent concentrations that are based on toxic end points. Bayesian benchmark dose methods are used to estimate points of departure and for estimating uncertainty factors (UFs) to develop preliminary OELs. These are then compared with epidemiological data to support the OEL and the use and magnitude of UFs, when appropriate.

[Determination of 1-chloro-2,3-epoxypropane in order to assess the working environment]. / Oznaczanie 1-chloro-2,3-epoksypropanu dla potrzeb oceny srodowiska pracy.

BACKGROUND: 1-Chloro-2,3-epoxypropane, known as epichlorohydrin (ECH), is a colorless liquid used in the production of epoxy resins, synthetic glycerine, elastomers, glycidyl ethers, surfactants, polyamide-epichlorohydrin resins and others. Epichlorohydrin may cause cancer. The aim of this study was to develop a new method for determining concentrations of ECH in workplace air in the range of 1/10-2 values of the maximum admissible concentration (MAC). MATERIAL AND METHODS: The paper presents a method for the determination of ECH in workplace air using a gas chromatograph coupled with a mass spectrometer (GC-MS). The developed method is based on the adsorption of ECH on an activated charcoal, extraction with acetone, and a chromatographic analysis of the resulting solution. RESULTS: The method developed makes it possible to determine ECH in the concentration range of 0.1-2 mg/m3, i.e., 1/10-2 values of MAC established in Poland. The limit of detection (LOD) is 0.24 µg/m3 and the limit of quantification (LOQ) is 0.71 µg/m3. CONCLUSIONS: The method is characterized by good precision and accuracy; it meets the requirements of the European standard PN-EN 482, and can be used by occupational hygiene laboratories to measure concentrations of ECH in workplace air, with a view to assessing workers' exposure to this substance. Med Pr. 2020;71(6):715-23.

Establishing a health-based recommended occupational exposure limit for nitrous oxide using experimental animal data - A systematic review protocol.

Nitrous oxide (N 2 O) is widely used as inhalation analgesic and anaesthetic in medical, paramedical, and veterinary practice. Previous evaluations resulted in classification of N 2 O as a possible risk factor for adverse reproductive health outcomes based on evidence from animal data. Available human data were considered inadequate, partly due to the possibility that other risk factors, such as co-exposures to other inhalation anaesthetics may have contributed to the adverse outcomes. As no substantial new human evidence has emerged since previous evaluations, this protocol describes a planned systematic review of the evidence obtained from animal studies. The aim is to assess the available evidence on the effects of N 2 O on reproductive and developmental outcomes in animals to inform a health-based recommended occupational exposure limit (OEL) for N 2 O. Comprehensive search strategies were designed to retrieve animal studies addressing N 2 O exposure from PubMed, EMBASE, and Web of Science. Screening of the studies retrieved will be performed by at least two independent reviewers, while discrepancies will be resolved by reaching consensus through repeated review and discussions. Articles will be included according to criteria specified in this protocol. Outcome data relevant for reproduction and development will be extracted and risk of bias will be assessed by two independent reviewers using the SYRCLE's risk of bias tool. Primary reproductive and developmental outcomes of interest will be the number of resorptions, malformations, and birth weight. We will focus on dose-response studies that allow to derive an OEL with the benchmark dose (BMD) approach. Adverse outcomes occurring at doses that are equivalent to the exposures occurring in human occupational settings will be particularly relevant for dose-response modelling. The proposed review has not been performed before. We will follow the procedures specified in this protocol. We will adhere to guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), adapted for animal studies. Ethical approval will not be required, as the review will use existing data available in the public domain.

Probabilistic risk assessment of occupational exposure to volatile organic compounds in the rendering plant of a poultry slaughterhouse.

In this study, occupational exposure to volatile organic compounds (VOCs) in the rendering plant of poultry slaughterhouse was determined and subsequently, carcinogen and non-carcinogenic risks were assessed using the US Environmental Protection Agency (USEPA). National Institute for Occupational Safety and Health (NIOSH) methods of 1501 and 1600 were used to measure VOCs in the breathing zone of the workers. Samples were analyzed by GC/MS. Carcinogenic and non-carcinogenic risks and sensitivity analysis were carried out using Monte Carlo simulations technique. The concentration of benzene and CS2 was higher than the occupational exposure limits (OEL). The hazard quotient (HQ) values for all measured compounds was more than 1, which indicating the high potential for non-carcinogenic risks. Furthermore, the calculated Lifetime Cancer Risks (LCR) for carcinogenic compounds revealed that cancer risk due to benzene is higher than the maximum acceptable level provided by USEPA (10-6). Based on the sensitivity analysis, the concentration and exposure frequency are the most important variable influencing both carcinogen and non-carcinogenic risks. Therefore, the concentration levels of the VOCs and exposure frequency should be controlled using engineering control measures.

Estimation of formaldehyde occupational exposure limit based on genetic damage in some Iranian exposed workers using benchmark dose method.

The present study evaluated an occupational exposure level for formaldehyde employing benchmark dose (BMD) approach. Dose-response relationship was determined by utilizing cumulative occupational exposure dose and DNA damage. Based on this goal, outcome of comet assay for some Iranian exposed people in occupational exposure individuals was used. In order to assess formaldehyde exposure, 53 occupationally exposed individuals selected from four melamine tableware workshops and 34 unexposed subjects as a control group were examined. The occupational exposure dose was carried out according to the NIOSH-3500 method, and the DNA damage was obtained by employing comet assay in peripheral blood cells. EPA Benchmark Dose Software was employed for calculating BMD and BMDL. Cumulative exposure dose of formaldehyde was between of 2.4 and 1972 mg. According to the findings of the current study, the induction of DNA damage in the exposed persons was increased tail length and tail moment (p < 0.001), when compared to controls. Finally, an acceptable dose-response relationship was obtained in three-category information between formaldehyde cumulative exposure doses and genetic toxicity. BMDL was 0.034 mg/m3 (0.028 ppm), corresponding to genetic damage of peripheral blood cells. It can be concluded that the occupational permissible limit in Iranian people could be at levels lower than OSHA standards.

Evaluation of airborne sensory irritants for setting exposure limits or guidelines: A systematic approach.

Sensory irritation of eyes and upper airways is an important endpoint for setting occupational exposure limits (OELs) and indoor air guidelines. Sensory irritants cause a painful burning, stinging and itching sensation. Controlled chamber studies are the "golden standard" for evaluations. Well conducted workplace studies offer another possibility. For generalization, the number of participants and their age, smoking, gender, and prior exposure, experience and mood has to be considered. Exposure assessments have to be reliable and exposure duration sufficiently long to establish time-response relationships. A potential confounding by odour has to be assessed. For workplace exposures, mixed exposure and healthy worker effects have to be evaluated. The "Alarie test" is the only validated animal bioassay for prediction of sensory irritation in humans. The mouse bioassay uses the trigeminal reflex-induced decrease in the respiratory rate. The 50% decrease (RD50) has been correlated with OELs set for sensory irritants; predicted OELs for sensory irritants are 0.03xRD50. Evaluation of the bioassay comprises the number of mice and the strain, the reliability of the exposure concentrations and exposure-response relationships, and the similar mode-of-action in mice and humans. These approaches can be used for quality assurance of reported data to set air quality guidelines.

The reciprocal calculation procedure for setting occupational exposure limits for hydrocarbon solvents: An update.

Hydrocarbon solvents are liquid hydrocarbon fractions, often with complex compositions. Due to the potential for human exposure, primarily to the more volatile solvents, substantial effort has been directed toward the development of occupational exposure recommendations. Because of the complex and variable nature of these substances, a proposed approach is to calculate occupational exposure levels (OELs) using an adaptation of the mixture formula developed by the ACGIH® in which "group guidance values" are assigned to similar constituents. This approach is supported by the results of toxicological studies of hydrocarbon solvents and their constituents which have shown that, with a few well-characterized exceptions, these substances have similar toxicological properties and produce additive effects. The objective of the present document is to summarize recommended revisions to the earlier proposals; these recommendations take into account recent toxicological information and changes in regulatory advice. Practical demonstrations on how to use these recommendations to develop occupational exposure advice in different situations (from simple complex solvents to blends of complex solvents) are also provided. Finally, a quantitative ideal gas method is proposed as a means of calculating occupational exposure limits for solvent blends in which, because the blended components have differing vapor pressures, there may be substantial differences between the liquid and vapor phase compositions.

Development of an occupational airborne chemical exposure matrix.

BACKGROUND: Population-based studies of the occupational contribution to chronic obstructive pulmonary disease generally rely on self-reported exposures to vapours, gases, dusts and fumes (VGDF), which are susceptible to misclassification. AIMS: To develop an airborne chemical job exposure matrix (ACE JEM) for use with the UK Standard Occupational Classification (SOC 2000) system. METHODS: We developed the ACE JEM in stages: (i) agreement of definitions, (ii) a binary assignation of exposed/not exposed to VGDF, fibres or mists (VGDFFiM), for each of the individual 353 SOC codes and (iii) assignation of levels of exposure (L; low, medium and high) and (iv) the proportion of workers (P) likely to be exposed in each code. We then expanded the estimated exposures to include biological dusts, mineral dusts, metals, diesel fumes and asthmagens. RESULTS: We assigned 186 (53%) of all SOC codes as exposed to at least one category of VGDFFiM, with 23% assigned as having medium or high exposure. We assigned over 68% of all codes as not being exposed to fibres, gases or mists. The most common exposure was to dusts (22% of codes with >50% exposed); 12% of codes were assigned exposure to fibres. We assigned higher percentages of the codes as exposed to diesel fumes (14%) compared with metals (8%). CONCLUSIONS: We developed an expert-derived JEM, using a strict set of a priori defined rules. The ACE JEM could also be applied to studies to assess risks of diseases where the main route of occupational exposure is via inhalation.

[Studies on an efficient method for determining 3,3'-dimethylbenzidine in the workplace air]. / Badania nad skuteczna metoda oznaczania 3,3'-dimetylobenzydyny w powietrzu na stanowiskach pracy.

BACKGROUND: 3,3'-Dimethylbenzidene (DMB) is a substance classified into the group of carcinogens. The value of maximum admissible concentration for this substance in the workplace air is not specified in Poland. Bearing in mind that DMB is used in domestic companies there is a need to develop a sensitive method for determining 3,3'-dimethylbenzidine in the work environment. MATERIAL AND METHODS: The method consists in passing DMB-containing air through sulfuric acid-treated glass fiber filters, washing out the substance settled on the filter, using water and solution of sodium hydroxide, liquid-liquid extraction with toluene, replacing dissolvent with acetonitrile and analyzing the obtained solution. Studies were performed using high-performance liquid chromatography (HPLC) technique. An Agilent Technologies chromatograph, series 1200, with a diode-array detector (DAD) and a fluorescence detector (FLD) was used in the experiment. In the test, an Ultra C18 column of dimensions: 250×4.6 mm, particle diameter (dp) = 5 µm (Restek) was applied. RESULTS: The method is linear (r = 0.999) within the investigated working range of concentration 1.08-21.6 µg/ml, which is equivalent to air concentrations 2-40 µg/m3 for a 540 l air sample. The limit of detection (LOD) of quantification determination is 5.4 ng/ml and the limit of quantification (LOQ) - 16.19 ng/ml. CONCLUSIONS: The analytical method described in this paper allows for selective determination of 3,3'-dimethylbenzidine in the workplace air in the presence of 1,4-phenylenediamine, benzidine, aniline, 3,3'-dimethoxybenzidine, 2-nitrotoluene, 3,3'-dichlorobenzidine and azobenzene. The method is characterized by good precision and good accuracy, it also meets the criteria for procedures involving the measurement of chemical agents, listed in EN 482:2012.

Methods to infer the compliance status with interval-averaged and with instantaneous occupational exposure limits from the results of longer-duration, integrated air sampling.

The duration of integrated air sampling for a substance may exceed the time frame of a substance's occupational exposure limit. Nonetheless, the compliance status of a limit may be inferred, under some circumstances, by the application of certain methods to the results of longer-duration samples. The purpose of this article is to define the inference methods and to illustrate their utility with actual and hypothetical examples. A review of articles and reports in U.S.-based Industrial Hygiene publications and databases revealed that the methods often were not but arguably should have been applied. Also revealed were inappropriate conclusions about the compliance status with exposure limits. Among the benefits of employing the inference methods is gaining information on exposures that might otherwise be overlooked. This article discusses the potential limitations of using the methods, and highlights some of the challenges of using integrated air sampling for assessing compliance with shorter-term exposure limits.

Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation.

The purpose of this article is to provide an overview and practical guide to occupational health professionals concerning the derivation and use of dose estimates in risk assessment for development of occupational exposure limits (OELs) for inhaled substances. Dosimetry is the study and practice of measuring or estimating the internal dose of a substance in individuals or a population. Dosimetry thus provides an essential link to understanding the relationship between an external exposure and a biological response. Use of dosimetry principles and tools can improve the accuracy of risk assessment, and reduce the uncertainty, by providing reliable estimates of the internal dose at the target tissue. This is accomplished through specific measurement data or predictive models, when available, or the use of basic dosimetry principles for broad classes of materials. Accurate dose estimation is essential not only for dose-response assessment, but also for interspecies extrapolation and for risk characterization at given exposures. Inhalation dosimetry is the focus of this paper since it is a major route of exposure in the workplace. Practical examples of dose estimation and OEL derivation are provided for inhaled gases and particulates.

[Occupational exposure to chromium(VI) compounds]. / Narazenie zawodowe na zwiazki chromu(VI).

This article discusses the effect of chromium(VI) (Cr(VI)) on human health under conditions of acute and chronic exposure in the workplace. Chromium(VI) compounds as carcinogens and/or mutagens pose a direct danger to people exposed to them. If carcinogens cannot be eliminated from the work and living environments, their exposure should be reduced to a minimum. In the European Union the proposed binding occupational exposure limit value (BOELV) for chromium(VI) of 0.025 mg/m³ is still associated with high cancer risk. Based on the Scientific Commitee of Occupational Exposure Limits (SCOEL) document chromium(VI) concentrations at 0.025 mg/m³ increases the risk of lung cancer in 2-14 cases per 1000 exposed workers. Exposure to chromium(VI) compounds expressed in Cr(VI) of 0.01 mg Cr(VI)/m3; is responsible for the increased number of lung cancer cases in 1-6 per 1000 people employed in this condition for the whole period of professional activity.

Analysis of workplace compliance measurements of asbestos by the U.S. Occupational Safety and Health Administration (1984-2011).

The United States Occupational Safety and Health Administration (OSHA) maintains the Chemical Exposure Health Data (CEHD) and the Integrated Management Information System (IMIS) databases, which contain quantitative and qualitative data resulting from compliance inspections conducted from 1984 to 2011. This analysis aimed to evaluate trends in workplace asbestos concentrations over time and across industries by combining the samples from these two databases. From 1984 to 2011, personal air samples ranged from 0.001 to 175 f/cc. Asbestos compliance sampling data associated with the construction, automotive repair, manufacturing, and chemical/petroleum/rubber industries included measurements in excess of 10 f/cc, and were above the permissible exposure limit from 2001 to 2011. The utility of combining the databases was limited by the completeness and accuracy of the data recorded. In this analysis, 40% of the data overlapped between the two databases. Other limitations included sampling bias associated with compliance sampling and errors occurring from user-entered data. A clear decreasing trend in both airborne fiber concentrations and the numbers of asbestos samples collected parallels historically decreasing trends in the consumption of asbestos, and declining mesothelioma incidence rates. Although air sampling data indicated that airborne fiber exposure potential was high (>10 f/cc for short and long-term samples) in some industries (e.g., construction, manufacturing), airborne concentrations have significantly declined over the past 30 years. Recommendations for improving the existing exposure OSHA databases are provided.

Derivation of an occupational exposure limit for inorganic borates using a weight of evidence approach.

Inorganic borates are encountered in many settings worldwide, spurring international efforts to develop exposure guidance (US EPA, 2004; WHO, 2009; ATSDR, 2010) and occupational exposure limits (OEL) (ACGIH, 2005; MAK, 2011). We derived an updated OEL to reflect new data and current international risk assessment frameworks. We assessed toxicity and epidemiology data on inorganic borates to identify relevant adverse effects. International risk assessment frameworks (IPCS, 2005, 2007) were used to evaluate endpoint candidates: reproductive toxicity, developmental toxicity, and sensory irritation. For each endpoint, a preliminary OEL was derived and adjusted based on consideration of toxicokinetics, toxicodynamics, and other uncertainties. Selection of the endpoint point of departures (PODs) is supported by dose-response modeling. Developmental toxicity was the most sensitive systemic effect. An OEL of 1.6mgB/m(3) was estimated for this effect based on a POD of 63mgB/m(3) with an uncertainty factor (UF) of 40. Sensory irritation was considered to be the most sensitive effect for the portal of entry. An OEL of 1.4mgB/m(3) was estimated for this effect based on the identified POD and an UF of 1. An OEL of 1.4mgB/m(3) as an 8-h time-weighted average (TWA) is recommended.

Workshop report: strategies for setting occupational exposure limits for engineered nanomaterials.

Occupational exposure limits (OELs) are important tools for managing worker exposures to chemicals; however, hazard data for many engineered nanomaterials (ENMs) are insufficient for deriving OELs by traditional methods. Technical challenges and questions about how best to measure worker exposures to ENMs also pose barriers to implementing OELs. New varieties of ENMs are being developed and introduced into commerce at a rapid pace, further compounding the issue of OEL development for ENMs. A Workshop on Strategies for Setting Occupational Exposure Limits for Engineered Nanomaterials, held in September 2012, provided an opportunity for occupational health experts from various stakeholder groups to discuss possible alternative approaches for setting OELs for ENMs and issues related to their implementation. This report summarizes the workshop proceedings and findings, identifies areas for additional research, and suggests potential avenues for further progress on this important topic.