The Experts below are selected from a list of 7164 Experts worldwide ranked by ideXlab platform
Andrew Maier - One of the best experts on this subject based on the ideXlab platform.
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an Occupational Exposure Limit oel approach to protect home healthcare workers exposed to common nebulized drugs
Regulatory Toxicology and Pharmacology, 2019Co-Authors: Evan A Frank, Andrew Maier, Simileoluwa Ishau, Susan Reutman, John F ReichardAbstract:Abstract Home healthcare is a growing area of employment. Assessment of Occupational health risks to home health care workers (HHCWs) is important because in many cases the unique characteristics of the home environment do not facilitate the level of Exposure control afforded to caregivers in hospitals and other fixed patient care sites. This assessment is focused on health risks to HHCWs from Exposure to pharmaceutical drugs used to treat asthma and other respiratory diseases, which are commonly administered to patients in aerosolized form via nebulizers. We developed risk-based Exposure Limits for workers in the form of Occupational Exposure Limits (OEL) values for Exposure to nebulized forms of the three most common drugs administered by this method: albuterol, ipratropium, and budesonide. The derived OEL for albuterol was 2 μg/day, for ipratropium was 30 μg/day, and for budesonide was 11 μg/day. These OELs were derived based on human effect data and adjusted for pharmacokinetic variability and areas of uncertainty relevant to the underlying data (human and non-human) available for each drug. The resulting OEL values provide an input to the Occupational risk assessment process to allow for comparisons to HHCW Exposure that will guide risk management and Exposure control decisions.
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Application of a framework for the selection of an appropriate Occupational Exposure Limit for manganese
Neurotoxicology, 2016Co-Authors: Michelle Deveau, Andrew Maier, Daniel KrewskiAbstract:Abstract Occupational Exposure Limits (OELs) serve as benchmarks for the interpretation of workplace Exposures within a health risk context. Different organizations derive OELs for many chemicals, including manganese. OELs recommended by different organizations can vary quantitatively, which can present a challenge to Occupational hygienists or other risk managers that need to select a value for decision-making purposes. In this article, we illustrate the application of a previously-developed OEL selection framework to demonstrate the decisions that would be required to select the most appropriate OEL for various manganese Exposure scenarios. The framework helped to identify the need to focus an evaluation on three quantitatively similar values—the ACGIH TLV, SCOEL IOELV, and DFG MAK. These values were compared with regulatory standards and considered for their relevance and reliability. The OEL selection framework was a useful tool in guiding the selection process for manganese OELs.
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The Scientific Basis of Uncertainty Factors Used in Setting Occupational Exposure Limits
Journal of Occupational and Environmental Hygiene, 2015Co-Authors: D A Dankovic, Andrew Maier, Michael Dourson, Bruce D Naumann, L S LevyAbstract:The uncertainty factor concept is integrated into health risk assessments for all aspects of public health practice, including by most organizations that derive Occupational Exposure Limits. The use of uncertainty factors is predicated on the assumption that a sufficient reduction in Exposure from those at the boundary for the onset of adverse effects will yield a safe Exposure level for at least the great majority of the exposed population, including vulnerable subgroups. There are differences in the application of the uncertainty factor approach among groups that conduct Occupational assessments; however, there are common areas of uncertainty which are considered by all or nearly all Occupational Exposure Limit-setting organizations. Five key uncertainties that are often examined include interspecies variability in response when extrapolating from animal studies to humans, response variability in humans, uncertainty in estimating a no-effect level from a dose where effects were observed, extrapolation f...
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derivation of an Occupational Exposure Limit for inorganic borates using a weight of evidence approach
Regulatory Toxicology and Pharmacology, 2014Co-Authors: Andrew Maier, Melissa J Vincent, E Hack, Patricia Nance, W BallAbstract:Abstract 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 1.6 mg B/m 3 was estimated for this effect based on a POD of 63 mg B/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 1.4 mg B/m 3 was estimated for this effect based on the identified POD and an UF of 1. An OEL of 1.4 mg B/m 3 as an 8-h time-weighted average (TWA) is recommended.
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Scientific Review of 1-Bromopropane Occupational Exposure Limit Derivations – Preliminary Thoughts and Areas for Further Analysis
2004Co-Authors: Toxicology Excellence, Risk Assessment, Andrew Maier, Michael DoursonAbstract:Current OELs for 1-bromopropane (1-BP) are diverse in both the selection of critical effects and judgments of remaining uncertainties. The resulting values differ by ~16-fold. We critically evaluated the underlying basis of existing OELs through the use of concepts such as critical effect, benchmark dose and uncertainty factor. We conclude that the critical effect is decreased live litter size with a BMDL of 190 ppm. Using an uncertainty factor of 10-fold, 3 for extrapolation from an animal study and 3 for human variability results in an OEL of 20 ppm
Leonard S. Levy - One of the best experts on this subject based on the ideXlab platform.
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Establishing an Occupational Exposure Limit for hexavalent chromium in the European Union.
Regulatory Toxicology and Pharmacology, 1997Co-Authors: Hilary J. Cross, Stephen P. Faux, Leonard S. LevyAbstract:Abstract A Criteria Document for hexavalent chromium [Cr(VI)], currently under preparation at the Institute of Occupational Health, University of Birmingham, is intended for use in setting an Occupational Exposure Limit (OEL) for Cr(VI) in the European Union (EU). The requirement for establishing OELs, specifically known as indicative Limit values, in the EU is set out in Council Directive 80/1107/EEC, amended by Council Directive 88/642/EEC. To facilitate this procedure the Commission has set up a Scientific Committee for Occupational Exposure Limits to Chemical Agents. The Committee, which is composed of independent scientific experts from member states, is responsible for reviewing available scientific data. A Criteria Document forms the basis of the scientific data considered during this process and contains an up-to-date, critical evaluation of available information which is relevant to setting an Exposure Limit. After consideration of the scientific data for a particular substance, the Committee advises the Commission on setting a health-based OEL. Consideration of other questions such as technical matters and socioeconomic issues occurs during later stages of the procedure, before an OEL is finally adopted. The procedure allows for consultation with interested parties. The Criteria Document for Cr(VI) contains sections on substance identification, chemical and physical properties, production and use data, recent data on Occupational Exposure, current methods for measurement and analysis, and toxicology. The toxicology section contains a critical evaluation of both human and animal data and forms a major part of the document. This section enables identification of critical health effects associated with Exposure to Cr(VI) and consideration of dose–response relationships and provides the basis for any risk assessment and recommendation for an OEL.
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The setting of an Occupational Exposure Limit for phosphamidon in the workplace--a Chinese approach.
The Annals of occupational hygiene, 1993Co-Authors: Jain-guo Zhuang, Yin-jiu Cheng, Si-xin Yang, Jia-hao Shu, Leonard S. LevyAbstract:This paper describes the approach of setting an Occupational Exposure Limit for phosphamidon, an organophosphorus pesticide, in the workplace in China. Apart from a general review of the literature relating to various toxicological studies, special emphasis has been placed on the results of a systematic Occupational health survey on the workers exposed to phosphamidon. As a result of the survey, together with the literature review, a 'maximum allowable concentration' (MAC) for phosphamidon in the air of workplace is suggested as 0.02 mg m-3 but on the condition that the route of skin entry be blocked effectively. In addition, based on the description of the standard-setting process in China, a comparison has been made to the current U.K. approach.
Wijnand Eduard - One of the best experts on this subject based on the ideXlab platform.
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fungal spores a critical review of the toxicological and epidemiological evidence as a basis for Occupational Exposure Limit setting
Critical Reviews in Toxicology, 2009Co-Authors: Wijnand EduardAbstract:Fungal spores are ubiquitous in the environment. However, Exposure levels in workplaces where mouldy materials are handled are much higher than in common indoor and outdoor environments. Spores of all tested species induced inflammation in experimental studies. The response to mycotoxin-producing and pathogenic species was much stronger. In animal studies, nonallergic responses dominated after a single dose. Allergic responses also occurred, especially to mycotoxin-producing and pathogenic species, and after repeated Exposures. Inhalation of a single spore dose by subjects with sick building syndrome indicated no observed effect levels of 4 x 10(3) Trichoderma harzianum spores/m(3) and 8 x 10(3) Penicillium chrysogenum spores/m(3) for lung function, respiratory symptoms, and inflammatory cells in the blood. In asthmatic patients allergic to Penicillium sp. or Alternaria alternata, lowest observed effect levels (LOELs) for reduced airway conductance were 1 x 10(4) and 2 x 10(4) spores/m(3), respectively. In epidemiological studies of highly exposed working populations lung function decline, respiratory symptoms and airway inflammation began to appear at Exposure levels of 10(5) spores/m(3). Thus, human challenge and epidemiological studies support fairly consistent LOELs of approximately 10(5) spores/m(3) for diverse fungal species in nonsensitised populations. Mycotoxin-producing and pathogenic species have to be detected specifically, however, because of their higher toxicity.
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fungal spores a critical review of the toxicological and epidemiological evidence as a basis for Occupational Exposure Limit setting
Critical Reviews in Toxicology, 2009Co-Authors: Wijnand EduardAbstract:Fungal spores are ubiquitous in the environment. However, Exposure levels in workplaces where mouldy materials are handled are much higher than in common indoor and outdoor environments. Spores of all tested species induced inflammation in experimental studies. The response to mycotoxin-producing and pathogenic species was much stronger. In animal studies, nonallergic responses dominated after a single dose. Allergic responses also occurred, especially to mycotoxin-producing and pathogenic species, and after repeated Exposures. Inhalation of a single spore dose by subjects with sick building syndrome indicated no observed effect levels of 4 × 10 3 Trichoderma harzianum spores/m 3 and 8 × 10
J.j. Van Hemmen - One of the best experts on this subject based on the ideXlab platform.
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Proposal for the assessment of quantitative dermal Exposure Limits in Occupational environments: Part 1. Development of a concept to derive a quantitative dermal Occupational Exposure Limit
Occupational and environmental medicine, 1998Co-Authors: P. M. J. Bos, Peter J Boogaard, Derk H. Brouwer, H. Stevenson, W.l.a.m. De Kort, J.j. Van HemmenAbstract:Dermal uptake of chemicals at the workplace may contribute considerably to the total internal Exposure and so needs to be regulated. At present only qualitative warning signs--the "skin notations"--are available as instruments. An attempt was made to develop a quantitative dermal Occupational Exposure Limit (DOEL) complementary to respiratory Occupational Exposure Limits (OELs). The DOEL refers to the total dose deposited on the skin during a working shift. Based on available data and experience a theoretical procedure for the assessment of a DOEL was developed. A DOEL was derived for cyclophosphamide and 4,4-methylene dianiline (MDA) according to this procedure. The DOEL for MDA was tested for applicability in an actual Occupational Exposure scenario. An integrated approach is recommended for situations in which both dermal and respiratory Exposures contribute considerably to the internal Exposure of the worker. The starting point should be an internal health based Occupational Exposure Limit--that is, the maximum dose to be absorbed without leading to adverse systemic effects. The proposed assessment of an external DOEL is then either based on absorption rate or absorption percentage. The estimation of skin penetration seems to be of crucial importance in this concept. If for a specific substance a maximal absorption rate can be estimated a maximal skin surface area to be exposed can be assessed which may then serve the purpose of a DOEL. As long as the actual skin surface exposed is smaller than this maximal skin surface area the internal OEL will not be exceeded, and therefore, no systemic health problems would be expected, independent of the dermal dose/unit area. If not, the DOEL may be interpreted as the product of dermal dose/unit area (mg/cm2) and exposed skin surface area (cm2). The proposed concept for a DOEL is relevant and can be made applicable for health surveillance in the Occupational situation where dermal Exposure contributes notably to the systemic Exposure. Further research should show whether this concept is more generally applicable.
Ester Lovsin Barle - One of the best experts on this subject based on the ideXlab platform.
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disease area and mode of action as criteria to assign a default Occupational Exposure Limit
Regulatory Toxicology and Pharmacology, 2021Co-Authors: Milica Glogovac, Caylee Paulson, Amy Lambert, Gian Christian Winkler, Ester Lovsin BarleAbstract:In the early stages of drug research and development, there are only a few or no toxicological data available for newly synthesized small molecule drug candidates (DC). Calculation of the DC's Occupational Exposure Limit (OEL) without toxicological data is not possible. Nevertheless, an OEL is needed to indicate the level of protection required to minimize risks for laboratory researchers and technicians. For this reason, simplified guidance is required to predict possible health hazards of DCs and their corresponding safe inhalation Exposure levels. Here, we evaluated 860 drug substances (DS) with OELs calculated by Novartis and grouped the DSs by disease area (DA) and then their mode of action (MoA). 28% of the evaluated DSs (n = 242) had an OEL <10 μg/m3 and 72% (n = 618) had an OEL ≥10 μg/m3. Our evaluation confirms that in the absence of any compound-specific data, the default OEL of 10 μg/m3 is a reasonably safe Exposure Limit for small molecule DCs. Furthermore, our analysis suggests certain DAs and MoAs as valid criteria that may be integrated into a company's specific strategy for the assessment of data-poor compounds in order to identify DCs in an early stage of their development which require a default OEL <10 μg/m3.
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Setting Occupational Exposure Limits for Genotoxic Substances in the Pharmaceutical Industry
Toxicological sciences : an official journal of the Society of Toxicology, 2016Co-Authors: Ester Lovsin Barle, Gian Christian Winkler, Susanne Glowienke, Azeddine Elhajouji, Jana Nunic, Hans-joerg MartusAbstract:In the pharmaceutical industry, genotoxic drug substances are developed for life-threatening indications such as cancer. Healthy employees handle these substances during research, development, and manufacturing; therefore, safe handling of genotoxic substances is essential. When an adequate preclinical dataset is available, a risk-based decision related to Exposure controls for manufacturing is made following a determination of safe health-based Limits, such as an Occupational Exposure Limit (OEL). OELs are calculated for substances based on a threshold dose-response once a threshold is identified. In this review, we present examples of genotoxic mechanisms where thresholds can be demonstrated and OELs can be calculated, including a holistic toxicity assessment. We also propose a novel approach for inhalation Threshold of Toxicological Concern (TTC) Limit for genotoxic substances in cases where the database is not adequate to determine a threshold.
