Deriving Compound-Specific Exposure Limits for Chemicals Used in Pharmaceutical Synthesis: Challenges in Expert Decision-Making Exemplified Through a Case Study-Based Workshop

2021 ◽  
pp. 109158182098254
Author(s):  
William C. Drewe ◽  
Krista L. Dobo ◽  
Zhanna Sobol ◽  
Joel P. Bercu ◽  
Patricia Parris ◽  
...  
Keyword(s):  
Expert Judgment ◽  
Decision Point ◽  
Exposure Limits ◽  
Genetic Toxicology ◽  
Decision Points ◽  
Exposure Limit ◽  
Risk Assessor ◽  
Common Observation ◽  
Degree Of Similarity

A workshop entitled “Deriving Compound-Specific Exposure Limits for Chemicals Used in Pharmaceutical Synthesis” was held at the 2018 Genetic Toxicology Association annual meeting. The objectives of the workshop were to provide an educational forum and use case studies and live multiple-choice polling to establish the degree of similarity/diversity in approach/opinion of the industry experts and other delegates present for some of the more challenging decision points that need to be considered when developing a compound-specific exposure limit (ie, acceptable intake or permissible or permitted daily exposure). Herein we summarize the relevant background and case study information for each decision point topic presented as well as highlight significant polling responses and discussion points. A common observation throughout was the requirement for expert judgment to be applied at each of the decision points presented which often results in different reasoning being applied by the risk assessor when deriving a compound-specific exposure limit. This supports the value of precompetitive cross-industry collaborations to develop compound-specific limits and harmonize the methodology applied, thus reducing the associated uncertainty inherent in the application of isolated expert judgment in this context. An overview of relevant precompetitive cross-industry collaborations working to achieve this goal is described.

scholarly journals Exposure of workers to occupational heat during the application of phytosanitary products in coffee crop

2020 ◽  
Vol 36 (4) ◽  
Author(s):  
Lucas Deleon Ramirio ◽  
Paulo Henrique Siqueira Sabino ◽  
Geraldo Gomes de Oliveira Júnior ◽  
Adriano Bortolotti da Silva ◽  
Wilson Roberto Pereira
Keyword(s):  
Thermal Stress ◽  
Occupational Exposure ◽  
Thermal Shock ◽  
Tolerance Limit ◽  
Occupational Exposure Limit ◽  
Exposure Limits ◽  
Exposure Limit ◽  
Phytosanitary Products

During the application of phytosanitary products in coffee trees, workers may be exposed to temperatures that could compromise their health. Exposure to occupational heat can lead to progressive dehydration, cramps, exhaustion and the possibility of thermal shock. Thus, knowing the levels of occupational heat that workers are exposed becomes important. This study aimed to evaluate workers’ occupational exposure to heat during the application of phytosanitary products with manual costal pump in the coffee crops. The case study was developed at the IFSULDEMINAS school farm - Campus Inconfidentes in the months of September and October 2017. The occupational heat in the coffee crop was evaluated using the WBGTAVERAGE method, using TGD 400 thermal stress meter. The WBGT values found were compared to the exposure limits of NR 15 for the purposes of insalubrity classification and with NHO 06 for acclimatized and non-acclimatized workers. The results showed that the WBGT found is below the tolerance limit of NR 15, for the month of September. In October, the tolerance limit was exceeded in the period from 11:00 a.m. to 2:59 p.m., considering a continuous heavy activity and rest in the workplace, and the activity considered unhealthy. Considering the criteria of the NHO 06 it was observed that the limits of occupational exposure were exceeded in the month of October, for acclimatized and non-acclimatized workers. In September the occupational exposure limit of NHO 06 was exceeded only for non-acclimated workers. Therefore, the workers should be submitted to acclimatization during the phytosanitary application activity in the month of October.

scholarly journals A Case Study of Brass Foundry Workers’ Estimated Lead (Pb) Body Burden from Different Exposure Routes

2020 ◽  
Vol 64 (9) ◽  
pp. 970-981
Author(s):  
Anneli Julander ◽  
Klara Midander ◽  
Sandra Garcia-Garcia ◽  
Per Vihlborg ◽  
Pål Graff
Keyword(s):  
Occupational Exposure ◽  
Numerical Control ◽  
Skin Absorption ◽  
Exposure Limits ◽  
Limit Values ◽  
Skin Exposure ◽  
Diffusion Cells ◽  
Exposure Limit ◽  
Exposure Routes

Abstract Objectives The most pronounced occupational exposure routes for lead (Pb) are inhalation and gastrointestinal uptake mainly through hand-to-mouth behaviour. Skin absorption has been demonstrated for organic Pb compounds, but less is known about inorganic Pb species. Several legislative bodies in Europe are currently proposing lowering biological exposure limit values and air exposure limits due to new evidence on cardiovascular effects at very low blood Pb levels. In light of this, all exposure routes in occupational settings should be revisited to evaluate how to lower the overall exposure to Pb. Methods The aim of the study was to investigate the possible exposure routes in workers operating computer numerical control-machines in a brass foundry and specifically to understand if metal cutting fluids (MCFs) used by the workers could lead to skin absorption of Pb. The different bronze alloys at the facility may contain up to 20% Pb. After obtaining written informed consent from the workers (n = 7), blood, skin wipes, and personal air samples were collected. In addition, MCFs used on the day of exposure measurements were collected for in vitro skin absorption studies using stillborn piglet skin mounted in static Franz diffusion cells (n = 48). All samples were analysed for Pb content using inductively coupled plasma mass spectrometry. Results Pb air concentration (<0.1–3.4 µg m−3) was well below the Swedish occupational exposure limit value. Blood Pb was in the range of <0.72–33 µg dl−1, and Pb on skin surfaces, after performing normal work tasks during 2 h, was in the range of 0.2–48 µg cm−2. Using the MCFs in diffusion cells showed that skin absorption had occurred at very low doses, and that up to 10% of the Pb content was present in the skin after 24 h exposure. Using these results in the US EPA adult lead model, we could estimate a contribution to blood Pb from the three exposure routes; where hand-to-mouth behaviour yielded the highest contribution (16 µg Pb dl−1 blood), followed by skin absorption (3.3–6.3 µg Pb dl−1 blood) and inhalation (2.0 µg Pb dl−1 blood). Conclusions This case study shows that MCF may lead to skin absorption of inorganic Pb and contribute to a systemic dose (quasi-steady state). Furthermore, even though good hand hygienic measures were in place, the workers’ skin exposure to Pb is in all likelihood an important contributor in elevating blood Pb levels. Skin exposure should thus be monitored routinely in workers at facilities handling Pb, to help reducing unnecessary occupational exposure.

When Scientific Knowledge and Ignorance Make It Difficult to Improve Occupational Health: A French and European Perspective

2021 ◽  
pp. 104829112110191
Author(s):  
Émilie Counil ◽  
Emmanuel Henry
Keyword(s):  
Occupational Health ◽  
Trade Unions ◽  
Public Health Intervention ◽  
Implementation Process ◽  
Health Issues ◽  
Political Debate ◽  
Exposure Limits ◽  
Attributable Fractions ◽  
Blind Spots

This article analyzes the consequences of the increasing reference to scientific expertise in the decision and implementation process of occupational health policy. Based on examples (exposure limits and attributable fractions) taken from an interdisciplinary seminar conducted in 2014 to 2015 in France, it shows how the measurement or regulation of a problem through biomedicine-based tools produces blind spots. It also uses a case study to show the contradictions between scientific and academic aims and public health intervention. Other indirect implications are also examined, such as the limitation of trade unions’ scope for action. Finally, the article suggests launching a broad political debate accessible to nonspecialists about collective occupational health issues—a dialogue made difficult by the rise of the afore-mentioned techno-scientific perspective.

A Methodology for the Test Design and Evaluation of Human Whole-Body Vibration in Ground Vehicle Systems

1989 ◽  
Vol 33 (18) ◽  
pp. 1192-1196
Author(s):  
Ellen C. Haas
Keyword(s):  
Whole Body Vibration ◽  
International Standards ◽  
Whole Body ◽  
Test Design ◽  
Exposure Limits ◽  
Ground Vehicle ◽  
Body Vibration ◽  
Exposure Limit ◽  
Vehicle Systems ◽  
Iso 2631

To date, testing and evaluation of whole-body vibration in ground vehicle systems have not always fully utilized appropriate experimental design methodology, applicable statistical tests, or relevant criteria. A test design and evaluation methodology was developed to eliminate these oversights. This methodology uses inferential statistics, questionnaires, and a comparison of vibration data with representative mission scenarios. The methodology was employed in the evaluation of two alternative tracked ground vehicle designs. The independent variables were track type, terrain, vehicle speed, and crew position. The dependent variables were International Standards Organization (ISO) 2631 whole-body vibration exposure limit times at the lateral, transverse, and vertical axes. Two different multivariate analyses of variance (MANOVAs) performed on the exposure limit data indicated that all main effects, as well as several interactions, were significant (p < .01). A comparison of exposure limits to a representative mission scenario indicated that both track types would exceed ISO 2631 exposure, comfort, and fatigue limits during expected travel over cross-country terrain. Crew questionnaires also indicated crew discomfort when exposed to this type of terrain. The experiment demonstrated that the procedure was useful in helping to determine the extent that vehicle vibration permits the performance of the vehicle mission, within limits dictated by safety, efficiency, and comfort.

scholarly journals Setting occupational exposure limits for antimicrobial agents: A case study based on a quaternary ammonium compound-based disinfectant

2020 ◽  
Vol 36 (9) ◽  
pp. 619-633
Author(s):  
G Scott Dotson ◽  
Jason T Lotter ◽  
Rachel E Zisook ◽  
Shannon H Gaffney ◽  
Andrew Maier ◽  
...  
Keyword(s):  
Occupational Exposure ◽  
Quaternary Ammonium ◽  
Antimicrobial Agents ◽  
Weight Of Evidence ◽  
Ammonium Compound ◽  
Occupational Exposure Limits ◽  
Exposure Limits ◽  
Viral Pathogen ◽  
Selection Of

Antimicrobial agents have become an essential tool in controlling the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and guidelines on their use have been issued by various public health agencies. Through its Emerging Viral Pathogen Guidance for Antimicrobial Pesticides, the US Environmental Protection Agency has approved numerous surface disinfectant products for use against SARS-CoV-2. Despite their widespread use and range of associated health hazards, the majority of active ingredients in antimicrobial products, such as surface disinfectants, lack established occupational exposure limits (OELs) to assist occupational health professionals in characterizing risks from exposures to these chemicals. Based on established approaches from various organizations, a framework for deriving OELs specific to antimicrobial agents was developed that relies on a weight-of-evidence evaluation of the available data. This framework involves (1) a screening-level toxicological assessment based on a review of the existing literature and recommendations, (2) identification of the critical adverse effect(s) and dose–response relationship(s), (3) identification of alternative health-based exposure limits (HBELs), (4) derivation of potential OELs based on identified points of departure and uncertainty factors and/or modification of existing alternative HBELs, and (5) selection of an appropriate OEL. To demonstrate the use of this framework, a case study is described for selection of an OEL for a disinfectant product containing quaternary ammonium compounds (quats). Three potential OELs were derived for this product based on irritation toxicity data, developmental and reproductive toxicity (DART) data, and modification of an existing HBEL. The final selected OEL for the quats-containing product was 0.1 mg/m3, derived from modification of an existing HBEL. This value represented the lowest resulting value of the three approaches, and thus, was considered protective of irritation and potential DART.

A Nascent Sport for Development and Peace Organization’s Response to Institutional Complexity: The Emergence of a Hybrid Agency in Kenya

2019 ◽  
Vol 33 (5) ◽  
pp. 450-466 ◽  
Author(s):  
Marlene A. Dixon ◽  
Per G. Svensson
Keyword(s):  
Local Community ◽  
Institutional Logics ◽  
Organizational Leaders ◽  
Institutional Complexity ◽  
Pivotal Moments ◽  
Formative Stage ◽  
Sport For Development ◽  
Decision Points ◽  
Case Organization

Sport for development and peace (SDP) agencies increasingly deal with complex institutional demands. In this article, the authors present an in-depth case study of how a nascent SDP organization created from within a local community in Kenya responded to institutional complexity through a series of pivotal moments that shaped the nature of the SDP agency. Throughout the formative stage in its life course, organizational leaders faced increased institutional complexity as they grappled with a series of incompatible prescriptions and demands from multiple institutional logics. The case organization—Highway of Hope—responded to this complexity through a process of organizational hybridity. Five pivotal decision points were identified and analyzed to explore how they shaped the organization over its early stages of existence. Our findings provide guidance for advancing our understanding of hybridity processes in SDP, both theoretically and practically.

Occupational Exposure Risk for Swine Workers in Confined Housing Facilities

2019 ◽  
Vol 25 (1) ◽  
pp. 37-50 ◽  
Author(s):  
Alvin C. Alvarado ◽  
Bernardo Z. Predicala
Keyword(s):  
Hydrogen Sulfide ◽  
Occupational Exposure ◽  
Weighted Average ◽  
Respirable Dust ◽  
Exposure Risk ◽  
Exposure Limits ◽  
Exposure Limit ◽  
Short Term Exposure ◽  
Swine Workers ◽  
Time Weighted Average

Abstract. Extended exposure of swine barn workers to noise and airborne contaminants has been reported to be associated with various health problems. In this study, the actual exposure of workers to respirable dust, gases (ammonia and hydrogen sulfide), and noise in swine production operations was monitored in order to determine the contribution of specific activities in the barn to potential adverse health impacts to swine workers. Selected workers in a swine barn facility were outfitted with a personal monitoring system that included a respirable dust sampler, ammonia (NH3) and hydrogen sulfide (H2S) gas monitors, and a noise dosimeter as they performed their regular duties during their workday. From a total of 50 monitoring days spanning winter and summer months, results showed that the occupational exposure of swine workers to respirable dust, NH3, H2S, and noise while performing their daily assigned tasks was generally below the respective time-weighted average exposure limits for each hazard. However, a number of tasks showed high likelihood for elevated occupational exposure risk. Respirable dust concentrations exceeded the time-weighted average limit of 3 mg m-3 while feeding and weighing pigs. These activities also exceeded the short-term exposure limit (35 ppm) for NH3. Dangerous levels of H2S were generated when draining manure from manure collection pits in the production rooms. Noise levels exceeded the recommended 15 min exposure limit (100 dBA) when weighing and loading pigs for market. The occupational exposure risks for workers to barn contaminants can be reduced through measures that control the generation of contaminants at their source, by removing generated contaminants from the work environment, as well as by outfitting the workers with protective devices that prevent personal exposure to contaminants. Keywords: Ammonia, Barn worker, Dust, Hydrogen sulfide, Noise, Occupational exposure, Risk, Swine.

scholarly journals A Human-Relevant 3D In Vitro Platform for an Effective and Rapid Simulation of Workplace Exposure to Nanoparticles: Silica Nanoparticles as Case Study

Nanomaterials ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1761 ◽  
Author(s):  
Luisana Di Cristo ◽  
Fabio Boccuni ◽  
Sergio Iavicoli ◽  
Stefania Sabella
Keyword(s):  
Silica Nanoparticles ◽  
Defense Mechanisms ◽  
Workplace Exposure ◽  
Limit Values ◽  
Limit Value ◽  
Exposure Limit ◽  
Airway Model

In this contribution, we show the suitability of a 3D airway model, when coupled with a nebulizer system, for simulating workplace exposure to nanoparticles. As a proof of concept, workplace exposure to silica nanoparticles was experimentally measured in an occupational facility where nanoparticles are produced weekly, and compared with the official limit value for bulk silica materials. These values of potential exposure were simulated in a 3D airway model by nebulizing low doses (from 0.90 to 55 µg/cm2) of silica nanoparticles over a prolonged period (12 weeks of repeated exposure, 5 days per week). Overall, the results suggest the efficiency of the defense mechanisms of the respiratory system and the clearance of the breathed silica nanoparticles by the mucociliary apparatus in accordance with the recent in vivo data. This in vitro platform shows that the doses tested may correlate with the occupational exposure limit values. Such relationship could provide regulatory-oriented data useful for risk classification of nanomaterials.

Nitroethane Documentation of proposed values of occupational exposure limits (OELs)

2017 ◽  
Vol 33 (1(91)) ◽  
pp. 97-113
Author(s):  
Andrzej Sapota ◽  
Małgorzata Skrzypińska-Gawrysiak ◽  
ANNA KILANOWICZ
Keyword(s):  
Occupational Exposure ◽  
The Body ◽  
Exposure Level ◽  
Occupational Exposure Limits ◽  
Exposure Limits ◽  
Short Term ◽  
Cellulose Esters ◽  
Limit Values ◽  
Exposure Limit ◽  
Short Term Exposure

Nitroethane is a colorless oily liquid with a mild fruity odor. It is used mainly as a pro-pellant (e.g., fuel for rockets), and as a solvent or dissolvent agent for cellulose esters, resins (vinyl and alkyd) and waxes, and also in chemical synthesis.Occupational exposure to nitroethane may occur during the process of its production and processing. There are no data on air concentra-tions of nitroethane in occupational exposure. In 2010–2015, workers in Poland were not exposed to nitroethane concentrations exceed-ing the maximum allowable value – 75 mg/m3 (the limit value valid since 2010).Nitroethane can be absorbed into the body via inhalation of its vapors or by ingestion.The discussed cases of nitroethane acute poi-soning caused by an accidental ingestion of artificial fingernail remover containing pure nitroethane concerned children under three years. Few hours after ingestion, cyanosis and sporadic vomiting were observed in children. The methemoglobin level reached 40÷50%.Neither data on chronic nitroethane poisoning in humans nor data obtained from epidemio-logical studies are available.On the basis of the results of acute toxicity studies nitroethane has been categorized in the group of hazardous compounds. However, eye and dermal irritation or allergic effects have not been evidenced. The studies of sub-chronic (4 and 90 days) and chronic (2 years) exposure to nitroethane per-formed on rats and mice (concentration range 310 ÷ 12 400 mg/m3) revealed the methemo-globinogenic effect of this compound and a minor damage to liver, spleen, salivary gland and nasal turbinates.Niroethane has shown neither mutagenic nor carcinogenic effects. Its influence on fertility has not been evidenced either. After chronic exposure (2 years) of rats to ni-troethane at concentration of 525 mg/m3 (the lowest observed adverse effect level – LOAEL), a slight change in a body mass of exposed fe-male animals and subtle changes in biochemi-cal parameters were observed, but there were no anomalies in hematological and histopatho-logical examinations.The value of 62 mg/m3 has been suggested to be adopted as the MAC value for nitroethane after applying the LOAEL value of 525 mg/m3 and relevant coefficients of uncertainty. The STEL value for nitroethane was proposed ac-cording to the methodology for determining short term exposure level value for irritating substances as three times MAC value (186 mg/m3) to prevent the effects of sensory irri-tations in humans. Because of its methemoglo-binogenic effect, 2% Met-Hb has been suggest-ed to be adopted as the value of biological ex-posure index (BEI), like the value already adopted for all methemoglobinogenic sub-stances.The Scientific Committee on Occupational Exposure Limits (SCOEL) proposed the time-weighted average (TWA) for nitroethane (8 h) as 62 mg/m3 (20 ppm), short-term exposure limit (STEL, 15 min) as 312 mg/m3 (100 ppm) and “skin” notation.Proposed OEL and STEL values for nitroethane were subjected to public consultation, con-ducted in 2011 by contact points, during which Poland did not raise any objections to the pro-posals. The proposed values for nitroethane by SCOEL has been adopted by the Advisory Committee on Safety and Health at Work UE (ACSH) and included in the draft directive establishing the IV list of indicative occupa-tional exposure limit values.

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