Approaches for setting occupational exposure limits in the pharmaceutical industry.

The use of pharmaceutical drugs has provided a cure for many diseases. However, unintended exposure to drugs in the manufacturing workplace can cause significant health hazards to workers. It is important to protect the workforce from these deleterious effects by limiting exposure to an acceptable level, the occupational exposure limit (OEL). OEL is defined as airborne concentrations (expressed as a time-weighted average for a conventional 8-h workday and a 40-h work week) of a substance to which nearly all workers may be repeatedly exposed (for a working lifetime) without adverse effects. Determination of OELs has become very challenging over time, requiring an overall assessment of the preclinical and clinical data of the drug being manufactured. Previously, to derive OEL values, toxicologists used animal no-observed-adverse-effect level (NOAEL) data, which have been replaced with the overall assessment of animal and human data, placing a higher emphasis on human health-based data. A major advantage of working with human pharmaceuticals is that sufficient clinical data are available for them in most cases. The present manuscript reviews the latest knowledge regarding the derivation of occupational exposure limits as health-based exposure limits (HBELs) for pharmaceuticals. We have provided examples of OEL calculations for various drugs including levofloxacin (CAS No. 100986-85-4), dienogest (CAS no. 65928-58-7), and acetylsalicylic acid (ASA, CAS no. 50-78-2) using human data. This report will benefit professionals in the OEL domain in understanding this highly important, growing, and challenging field.

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.

Investigation of radiation protection and safety measures in Rwandan public hospitals: Readiness for the implementation of the new regulations.

BACKGROUND: An essential concept that all radiographers are required to implement is the use of techniques and the provision of protective devices to minimize radiation to patients and staff. Methods to achieve this could include good communication, immobilization, beam limitation, justification for radiation exposure, shielding, appropriate distances and optimum radiographic exposures factors. PURPOSE: The aim of this study was to assess the availability and utilization of radiation protection and safety measures by medical imaging technologists (MITs) in Rwandan hospitals. METHODS: A quantitative, non-experimental descriptive design was used and data collected by means of a self-designed questionnaire. One hundred and sixteen MITs (n = 116) representing 96.67% of the total population participated in the study. RESULTS: The study found radiation safety measures were not adequately implemented in government hospitals. Only 58.62% of MITs had radiation-measuring devices, with 29% receiving dose readings inconsistently. Lead rubber aprons were available at 99.13% of the hospitals; however, 59% of the participants had never checked the integrity of the aprons. Lead rubber aprons and lead equivalent barriers were most prevalent in the facilities. CONCLUSION: The study found there was a lack of adequate radiation safety equipment. Exposure charts and immobilization devices were not adequately implemented in the hospitals. The level of education and experience of the MITs did not appear to influence the radiation safety practice significantly. There is a need for concerted efforts between the Rwanda Utilities Regulatory Authority (RURA), Ministry of Health, University of Rwanda and hospital management to improve the radiation safety culture, especially in view of the law governing radiation protection that was recently promulgated.

International landscape of limits and recommendations for occupational exposure to engineered nanomaterials.

The increasing concern of possible adverse effects on human health derived from occupational engineered nanomaterials (ENMs) exposure is an issue addressed by entities related to provide guidelines and/or protocols for ENMs regulation. Here we analysed 17 entities from America, Europe and Asia, and some of these entities provide limits of exposure extrapolated from the non-nanosized counterparts of ENMs. The international landscape shows that recommendations are mostly made for metal oxide based ENMs and tonnage is one of the main criteria for ENMs registration, however, sub-nanometric ENMs are emerging and perhaps a novel category of ENMs will appear soon. We identify that besides the lack of epidemiological evidence of ENMs toxicity in humans and difficulties in analysing the toxicological data derived from experimental models, the lack of information on airborne concentrations of ENMs in occupational settings is an important limitation to improve the experimental designs. The development of regulations related to ENMs exposure would lead to provide safer work places for ENMs production without delaying the nanotechnology progress but will also help to protect the environment by taking opportune and correct measures for nanowaste, considering that this could be a great environmental problem in the coming future.

Surgical Smoke-Hazard Perceptions and Protective Measures in German Operating Rooms.

(1) Background: Hazardous substances in surgical smoke that is generated during laser or electrosurgery pose a potential health hazard. In Germany, the Technical Rules for Hazardous Substances (TRGS 525) have included recommendations for appropriate protective measures since 2014. Up to now, no empirical data has been available on the extent to which recommendations have been implemented in practice. (2) Methods: In 2018, 7089 surgeons in hospitals and outpatient practices were invited by email to participate in an online survey. In addition, 219 technical assistants were interviewed. The questionnaire dealt with knowledge of, and attitudes toward, the hazard potential of surgical smoke, as well as the availability and actual use of protective measures. Furthermore, manufacturers and distributors of smoke extraction devices were asked to give their assessment of the development of prevention in recent years. (3) Results: The survey response rate was 5% (surgeons) and 65% (technical assistant staff). Half of all surgeons assumed that there were high health hazards of surgical smoke without taking protective measures. Operating room nurses were more often concerned (88%). Only a few felt properly informed about the topic. The TRGS recommendations had been read by a minority of the respondents. In total, 52% of hospital respondents and 65% of the respondents in outpatient facilities reported any type of special suction system to capture surgical smoke. One-fifth of respondents from hospitals reported that technical measures had improved since the introduction of the TRGS 525. Fifty-one percent of the surgeons in hospitals and 70% of the surgeons in outpatient facilities "mostly" or "always" paid attention to avoiding surgical smoke. The most important reason for non-compliance with recommendations was a lack of problem awareness or thoughtlessness. Twelve industrial interviewees who assessed the situation and the development of prevention in practice largely confirmed the prevention gaps observed; only slight developments were observed in recent years. (4) Conclusions: The low response rate among surgeons and the survey results both indicate a major lack of interest and knowledge. Among other measures, team interventions with advanced training are needed in the future.

Surgical smoke: articulating the problem.

This six-part series focuses on surgical smoke evacuation legislation and policy. It provides answers to important frequently asked questions (FAQs) about surgical smoke from policymakers and people not working in perioperative services and suggests resources and tools to help you become a strong advocate for surgical smoke evacuation. The FAQs and legislative checklists that will be shared will cover the basics of surgical smoke and its harmful effects, strategies and solutions for eradicating surgical smoke in the OR, the role of regulatory agencies, and how to lay the groundwork for successful state legislation on your own and in tandem with AORN's Government Affairs Department.

[Priority: safe working conditions]. / Priorytet: bezpieczne warunki pracy.

The drawing up of a new regulation of the Minister of Family, Labour and Social Policy regarding the maximum admissible concentrations and intensities of agents harmful to health in the working environment resulted from the obligatory implementation into national law the provisions of Commission Directive (EU) 2017/164 of 31 January 2017 establishing a fourth list of indicative occupational exposure limit values pursuant to Council Directive 98/24/EC, and amending Commission Directives 91/322/EEC, 2000/39/EC and 2009/161/EU, the provisions of which Member States had to introduce by 21 August 2018, and partly Directive 2017/2398/EU of the European Parliament and of the Council of 12 December 2017 amending Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work. The Regulation takes into account 13 applications submitted in the years 2014-2017 by the Interdepartmental Commission for Maximum Admissible Concentrations and Intensities for Agents Harmful to Health in the Working Environment to the minister competent for labour issues. The Commission was appointed by way of the regulation of the Prime Minister of 15 December 2008 (Journal of Laws 2015, item 1772, as amended), and its tasks include submitting to the minister competent for labour issues applications regarding the value of the maximum admissible concentrations and intensities for agents harmful to health in the working environment. Med Pr. 2019;70(4):497-509.

[The "new carcinogens' directive" from the European Union: new tasks waiting for us, new opportunities in front of us (and that we need not to waste) in Italy]. / La "nuova direttiva cancerogeni" dell'Unione Europea: gli impegni che ci attendono, le nuove opportunità che ci si presentano (e non dobbiamo sprecare) in Italia.

SUMMARY: The new EU directive on the protection of workers from the risks related to exposure to carcinogens and mutagens at work, issued on December 2017, will be integrated inside the Member States' national laws not later than 17th January 2020. The new directive brings in force new binding occupational exposure limit values (BOELVs) for several agents, some of great importance such as hard wood dusts, a set of hexavalent chromium compounds and crystalline silica dust; for some cases, the entry into force of the new limits is delayed in time. The new directive clarifies that the limit values are established considering factors distinct from health necessities too. The Member States are bound to adopt national limit values not avexceeding the corresponding EU ones, but are empowered to lower them. It is essential that the control of the actual respect of the limit values results not only from the application of theoretic previsional models, but is entrusted mainly to high quality exposure measurements and to estimates directly derived from measurements, on the base of publicly available JEMs. The specific health surveillance to be provided to any person both exposed and previously exposed to carcinogens at work should not be limited to proper oncological screening actions, but should include programs for biological monitoring of both exposures and related pre-neoplastic effects, every time any of these is possible and useful. A fair mapping of the exposures to carcinogens and mutagens at work and a systematical registration of cases of cancers attributable to occupational exposures will be placed side to side.

Will worker DNELs derived under the European REACH regulation extend the landscape of occupational exposure guidance values?

Derived no-effect levels for workers (wDNELs) under the European REACH legislation have many aspects in common with occupational exposure limits (OELs). In an attempt to examine under which circumstances wDNELs might be used as exposure guidance outside their intended application, we compared derivation methods, coverage of substances and numerical values of wDNELs against two regulatory OEL lists (European Commission and Sweden) and three sets of recommendations (European SCOEL, German MAK and US ACGIH). Finally, we looked closer at wDNELs where SCOEL concluded that data were insufficient to derive an OEL. Major differences between wDNELs and OELs include regulatory background, intended use, actors involved, substance selection criteria, transparency and procedure of derivation, and operationalisation in terms of risk management measures. As of summer 2018, approximately five times more substances were covered by wDNELs than by the five sets of OELs examined herein. Meanwhile, many occupationally relevant pollutants were not covered by wDNELs, e.g. one-third of Swedish OELs lack corresponding wDNELs. We also note that wDNELs and OELs for the same substance may vary considerably, up to several orders of magnitude. In conclusion, with extensive substance coverage, wDNELs extend the landscape beyond the OELs. That said, important limitations are (1) that many air pollutants relevant for workers' health are not covered by REACH, and (2) concerns for inconsistencies in the derivation of wDNELs and in their level of protection. In particular, that route-to-route extrapolation is a common practice that may be grossly misleading when the effect of concern is local, e.g. sensitisation.

Practical recommendations for the application of DE 59/2013.

The changes introduced with Council Directive 2013/59/Euratom will require European Member States adapt their regulations, procedures and equipment to the new high standards of radiation safety. These new requirements will have an impact, in particular, on the radiology community (including medical physics experts) and on industry. Relevant changes include new definitions, a new dose limit for the eye lens, non-medical imaging exposures, procedures in asymptomatic individuals, the use and regular review of diagnostic reference levels (including interventional procedures), dosimetric information in imaging systems and its transfer to the examination report, new requirements on responsibilities, the registry and analysis of accidental or unintended exposure and population dose evaluation (based on age and gender distribution). Furthermore, the Directive emphasises the need for justification of medical exposure (including asymptomatic individuals), introduces requirements concerning patient information and strengthens those for recording and reporting doses from radiological procedures, the use of diagnostic reference levels, the availability of dose-indicating devices and the improved role and support of the medical physics experts in imaging.

A case from India of pleural malignant mesothelioma probably due to domestic and environmental asbestos exposure: a posthumous report.

India is the largest consumer of asbestos in the world. There is no report from India of mesothelioma related to asbestos. The case is a 42-year-old man who died of pleural mesothelioma. He was exposed to asbestos domestically and from the environment since birth. Two of his close family members worked in a factory that used asbestos. The living quarter of the family was within the premises of the factory. Asbestos waste was strewn on the grounds surrounding the quarters. After decades of legal battles by workers and families exposed to asbestos, Indian courts have ordered remedial measures and compensation to people, who are exposed to asbestos at work and the environment. Mesothelioma, currently in epidemic proportions in the west where asbestos production was banned in the 1990s, could rise to alarming levels in the next decades in India if the legal remedial measures are not implemented soon.

The new lens dose limit: implication for occupational radiation protection.

AIM AND OBJECTIVES: The aim of this article was to explore the implications of the new Euratom dose limit for occupational radiation protection in the context of medical occupational radiation exposures. The European Directive 2013/59/Euratom takes into account the new recommendations on reduction in the dose limit for the lens of the eye for planned occupational exposures released in 2012 by the International Commission on Radiological Protection (ICRP 118). MATERIALS AND METHODS: Different dose-monitoring procedures and devices were considered. Occupational eye lens doses reported by previous studies were analyzed, mainly considering workers involved in interventional procedures with X-rays. The current status of eye lens radiation protection and the main methods for dose reduction were investigated. RESULTS: The analysis showed that the workers, potentially exceeding the new limit, are clinical staff performing interventional procedures with a relatively high X-ray dose. Regarding radiological protection issues, the considered literature reports that the proper use of personal protective equipment may reduce the eye lens absorbed dose. CONCLUSION: The evaluation of the occupational eye lens dose is essential to establish which method of personal dose monitoring should be preferred. Furthermore, education and training about the right use of personal protective equipment are important for medical staff working with ionizing radiation.

A European survey on the regulatory status for the estimation of the effective dose and the equivalent dose to the lens of the eye when radiation protection garments are used.

Following the proposal of the ICRP for the reduction of the dose limit for the lens of the eye, which has been adopted by the International Atomic Energy Agency and the European Council, concerns have been raised about the implementation of proper dose monitoring methods as defined in national regulations, and about the harmonisation between European countries. The European Radiation Dosimetry Group organised a survey at the end of 2017, through a web questionnaire, regarding national dose monitoring regulations. The questions were related to: double dosimetry, algorithms for the estimation of the effective dose, methodology for the determination of the equivalent dose to the lens of the eye and structure of the national dose registry. The results showed that more than 50% of the countries that responded to the survey have legal requirements about the number and the position of dosemeters used for estimation of the effective dose when radiation protection garments are used. However, in only five out of 26 countries are there nationally approved algorithms for the estimation of the effective dose. In 14 out of 26 countries there is a legal requirement to estimate the dose to the lens of the eye. All of the responding countries use some kind of national database for storing individual monitoring data but in only 12 out of 26 countries are the estimated effective dose values stored. The personal dose equivalent at depth 3 mm is stored in the registry of only seven out of 26 countries. From the survey, performed just before the implementation of the European Basic Safety Standards Directive, it is concluded that national occupational exposure frameworks require intensive and immediate work under the coordination of the competent authorities to bring them into line with the latest basic safety standards and achieve harmonisation between European countries.

Arsenic Exposure, Assessment, Toxicity, Diagnosis, and Management: Guidance for Occupational and Environmental Physicians.

: Arsenic is ubiquitous in the environment and human exposure can occur from multiple possible routes including diet. Occupational medicine physicians asked to evaluate workers with elevated urine arsenic levels may be unaware that many sources of arsenic exposure are not work related. In this paper, we address arsenic exposure sources and pathways, adverse health effects of arsenic exposure and those subpopulations at increased risk, and the evaluation and treatment of those exposed to elevated arsenic levels.