Setting Of Occupational Exposure Limits Research Articles

Evaluation of Risk and Uncertainty for Model-Predicted NOAELs of Engineered Nanomaterials Based on Dose-Response-Recovery Clusters

Abstract Experimental toxicology studies for the purposes of setting occupational exposure limits for aerosols have drawbacks including excessive time and cost which could be overcome or limited by the development of computational approaches. A quantitative, analytical relationship between the characteristics of emerging nanomaterials and related in vivo toxicity can be utilized to better assist in the subsequent mitigation of exposure toxicity by design. Predictive toxicity models can be used to categorize and define exposure limitations for emerging nanomaterials. Model-based no-observed-adverse-effect-level (NOAEL) predictions were derived for toxicologically distinct nanomaterial clusters, referred to as model-predicted no observed adverse effect levels (MP-NOAELs). The lowest range of MP-NOAELs for the polymorphonuclear neutrophil (PMN) response observed by carbon nanotubes (CNTs) was found to be 21–35 μg/kg (cluster “A”), indicating that the CNT belonging to cluster A showed the earliest signs of adverse effects. Only 25% of the MP-NOAEL values for the CNTs can be quantitatively defined at present. The lowest observed MP-NOAEL range for the metal oxide nanoparticles was Cobalt oxide nanoparticles (cluster III) for the macrophage (MAC) response at 54–189 μg/kg. Nearly 50% of the derived MP-NOAEL values for the metal oxide nanoparticles can be quantitatively defined based on current data. A sensitivity analysis of the MP-NOAEL derivation highlighted the dependency of the process on the shape and type of the fitted dose-response model, its parameters, dose selection and spacing, and the sample size analyzed.

The difficulties in establishing an occupational exposure limit for carbon nanotubes

Concern over the health effects from the inhalation of carbon nanotubes (CNTs) has been building for some time, and adverse health effects found in animal studies include acute and chronic respiratory damage, cardiac inflammation, and cancer including mesothelioma, heretofore only associated with asbestos exposure. The strong animal evidence of toxicity requires that the occupational hygiene community develops strategies for reducing or eliminating worker exposures to CNTs; part of this strategy involves the setting of occupational exposure limits (OELs) for CNTs. A number of government agencies and private entities have established OELs for CNTs; some are mass-based, while others rely on number concentration. We review these various proposed standards and discuss the pros and cons of each approach. We recommend that specific action be taken, including intensified outreach to employers and employees concerning the potential adverse health effects from CNT inhalation, the development of more nuanced OELs that reflect the complex nature of CNT exposure, a broader discussion of these issues among all interested parties, and further research into important unanswered questions including optimum methods to evaluate CNT exposures. We conclude that current animal toxicity evidence suggests that strong action needs to be taken to minimize exposures to CNTs, and that any CNT OEL should be consistent with the need to minimize exposures.

Group assessment of drug substances with same mechanism of action and safety profile for purpose of setting occupational exposure limits

Group assessment of drug substances with same mechanism of action and safety profile for purpose of setting occupational exposure limits

Measures of odor and lateralization thresholds of acrolein, crotonaldehyde, and hexanal using a novel vapor delivery technique.

IntroductionHumans are exposed to aldehydes in a variety of environmental situations. Aldehydes generally have a strong odor and are highly irritating to the mucous membranes. Knowledge about odor perception and especially irritation potency in humans is thus essential in risk assessment and regulation, e.g. setting occupational exposure limits. However, data on odor and irritation are lacking or limited for several aldehydes. The aim of the study was to determine the odor and lateralization thresholds of some commonly occurring aldehydes. Acrolein and crotonaldehyde where chosen as they are formed when organic material is heated or burned, e.g. during cigarette smoking. n-Hexanal was also included as it is emitted from wood pellets and fibreboard.Material and methodsTo study odor and lateralization thresholds of these aldehydes, a novel, inexpensive olfactometer was designed to enable delivery of reliable and stable test concentrations and thus valid measures of thresholds. The delivery system consists of seven syringe pumps, each connected to a Tedlar bag containing a predefined concentration of the tested aldehyde vapor. To validate the threshold measures, a test-retest was performed with a separate method, namely odor delivery via amber bottles. Twenty healthy naïve individuals were tested.ResultsThe median odor thresholds of acrolein, crotonaldehyde and hexanal were 17, 0.8, and 97 ppb, respectively. No lateralization threshold could be identified for acrolein (highest tested concentration was 2 940 ppb in 5 subjects), whereas the medians were 3 and 390 ppb for the latter two. In addition, odor thresholds for n-hexanal were also determined using two methods where similar results were obtained, suggesting that the olfactometer presentation method is valid.ConclusionWe found olfactory detection and lateralization thresholds (except for acrolein) in alliance with, or lower than, previously reported in naïve subjects. The new olfactometer allows better control of presentations timing and vapor concentration.

Systems Biology and Biomarkers of Early Effects for Occupational Exposure Limit Setting

In a recent National Research Council document, new strategies for risk assessment were described to enable more accurate and quicker assessments.(1) This report suggested that evaluating individual responses through increased use of bio-monitoring could improve dose-response estimations. Identi-fication of specific biomarkers may be useful for diagnostics or risk prediction as they have the potential to improve exposure assessments. This paper discusses systems biology, biomarkers of effect, and computational toxicology approaches and their relevance to the occupational exposure limit setting process.The systems biology approach evaluates the integration of biological processes and how disruption of these processes by chemicals or other hazards affects disease outcomes. This type of approach could provide information used in delineating the mode of action of the response or toxicity, and may be useful to define the low adverse and no adverse effect levels. Biomarkers of effect are changes measured in biological systems and are considered to be preclinical in nature. Advances in computational methods and experimental -omics methods that allow the simultaneous measurement of families of macromolecules such as DNA, RNA, and proteins in a single analysis have made these systems approaches feasible for broad application.The utility of the information for risk assessments from -omics approaches has shown promise and can provide information on mode of action and dose-response relationships. As these techniques evolve, estimation of internal dose and response biomarkers will be a critical test of these new technologies for application in risk assessment strategies. While proof of concept studies have been conducted that provide evidence of their value, challenges with standardization and harmonization still need to be overcome before these methods are used routinely.

Nanotoxicology: in Vitro–in Vivo Dosimetry

Nanotoxicology: in Vitro–in Vivo Dosimetry

Comparing the safety margins in the European indicative occupational exposure limits and the derived no-effect levels under reach

The new European Union (EU) REACH legislation requires Derived No-Effect Levels (DNEL) to be calculated for substances produced in quantities above 10 tonnes/year. Workers are one population that these DNELs are to protect. Meanwhile, the setting of occupational exposure limits (OEL) continues both at the member state and the EU level. Health-based OELs are proposed by the Commission's Scientific Committee on OELs (SCOEL) and eventually result in Indicative OEL Values (IOELV) in EU Directives. According to REACH, IOELVs may under some circumstances be used as worker-DNELs. On the other hand, worker-DNELs will be derived for several thousand substances, far more than the roughly 100 substances for which IOELVs have been established. Thus, the procedure to set health-based OELs may become influential on that of DNELs and vice versa. This study presents a comparison of the safety margins of 88 SCOEL recommendations with those of the corresponding worker-DNELs, derived according to the REACH guidance document. Overall, the REACH safety margins were approximately six times higher than those derived from the SCOEL documentation but varied widely with REACH/SCOEL ratios ranging by two orders of magnitude, from 0.3 to 58. It was also found that the REACH guidance document, although encompassing detailed advice on many issues, including default assessment factors for species and route extrapolation, gives no quantitative guidance on when and how to depart from defaults.

A Quantitative Comparison of the Safety Margins in the European Indicative Occupational Exposure Limits and the Derived No-Effect Levels for Workers under REACH

The new European Union (EU) REACH legislation requires derived no-effect levels (DNELs) to be calculated for substances produced in quantities above 10 tonnes/year. Meanwhile, the setting of occupational exposure limits (OELs) continues both at the member state and the EU levels. According to REACH, indicative OEL values (IOELVs) from the Commission may under some circumstances be used as worker-DNELs. On the other hand, worker-DNELs will be derived for several thousand substances, far more than the approximately 100 substances for which IOELVs have been established. Thus, the procedure to set health-based OELs may become influential on that of DNELs and vice versa. In this study, we compare the safety margins of 88 Scientific Committee on OELs (SCOEL) recommendations with those of the corresponding worker-DNELs, derived according to the default approach as described in the REACH guidance document. Overall, the REACH safety margins were approximately six times higher than those derived from the SCOEL documentation but varied widely with REACH/SCOEL safety margin ratios ranging by two orders of magnitude, from 0.3 to 58 (n = 88). The discrepancies may create confusion in terms of legal compliance, risk management, and risk communication. We also found that the REACH guidance document, although encompassing detailed advice on many issues, including default assessment factors for species and route extrapolation, gives little quantitative guidance on when and how to depart from defaults.

Bitumen: a challenge for toxicology and occupational health

Setting of occupational exposure limits (OEL) for bitumen is currently on the agenda of regulatory bodies internationally. Bitumen is mainly used in paving and rooWng applications. Its chemical composition is variable and depends on the composition of the underlying crude oil and the manufacturing process. Bitumen consists mainly of aliphatic compounds, aromatic hydrocarbons, heterocyclic compounds containing nitrogen, oxygen, and sulfur atoms, and small amounts of polycyclic aromatic hydrocarbons (PAH). Depending on the type of bitumen and its laying temperature, workers are exposed to diVerent quantities of various bitumen constituents, with varying concentrations of vapors and aerosols. The complex composition is one of the reasons why investigations, which may serve as a basis for occupational standard setting, are scarce. Another reason is the diYculty to organize Weld studies with a suYciently large number of exposed persons, when the working places and associated working conditions are highly variable. Therefore, investigations into the health eVects of occupational bitumen exposure have been remained a major scientiWc challenge. Bitumen for long has been regarded as possible carcinogen because of its contents of polycyclic aromatic hydrocarbons (PAH). For instance, the German MAK commission had classiWed bitumen as a suspected carcinogen (K3) already in the 1980s, and a health-based OEL was not derived (Greim 2001). Instead, the German tripartide Committee for Hazardous Substances (AGS) had set a TRK value (Technical Guidance Concentration), which reXects the technically manageable exposure. A classiWcation of bitumen as carcinogenic was seemingly conWrmed by positive carcinogenicity results of a long-term bioassay using dermal application (Sivak et al. 1997). In Germany, these Wndings led to lowering of the TRK value, which was Wnally suspended by end of 2004. Industry, however, argued that the route of administration in the dermal bioassay did not reXect the occupational exposure. Therefore, new studies were initiated to further clarify the situation. A long-term inhalation carcinogenicity study in rats turned out to be negative (Fuhst et al. 2007), and substantial eVorts were made to gain sustainable data on human health from exposed persons. Missing data on possible respiratory eVects were of particular interest. So far, only few studies have characterized the eVects of bitumen exposure on nonmalignant responses of the respiratory tract, and especially data on irritative eVects of bitumen under current exposure conditions in humans remained limited. This situation led to the initiation of a new occupational study in mastic asphalt workers exposed to vapors and aerosols of bitumen under current exposure conditions. The principal aim of this large-scale Human Bitumen Study in Germany was to assess irritative eVects of vapors and aerosols on the airways, using a cross-shift design in a wellcharacterized group of bitumen-exposed workers. Furthermore, it appeared worthwhile to use the study to determine possible genotoxic eVects in blood cells. With the examination of 500 workers, the new Human Bitumen Study is one of the largest investigations of bitumen-exposed workers under current working conditions. The results of these studies are important, if new OELs will be considered. The project is an example of successful collaboration of diVerent disciplines, namely occupational hygienists and physicians, pneumologists, immunologists, epidemiologists, and toxicologists. In this supplemental issue of G. Schluter (&) Wuppertal, Germany e-mail: gerhard.schlueterGS1@gmx.net

Neuromotor effects of short‐term and long‐term exposures to trichloroethylene in workers

Health effects of long-term exposure to organic solvents at low levels are a major concern in industrialized countries. To assess the neuromotor impact of trichloroethylene objectively, static postural sway and hand tremor parameters, along with urinary trichloroethanol (TCOH) and trichloroacetic acid (TCAA) levels, were investigated in 57 workers without obvious neurological disorders and 60 control subjects. The workers had been occupationally exposed to trichloroethylene for 0.1-37 years. The cumulative exposure index (CEI) was calculated from their occupational history and total trichloro-compounds (TCOH + TCAA). Median levels in the workers were 1.7 mg/L for TCOH and 2.5 mg/L for TCAA, and the maximum ambient trichloroethylene concentration was estimated to be <22 ppm from the previously reported equation using TCOH + TCAA. Sway parameters with eyes open and tremor intensity in dominant hand were significantly larger in the exposed workers than in the control subjects when adjusting for possible confounders. A significant dose-effect association was seen between two sway parameters and urinary TCOH level in the workers. Tremor intensities in non-dominant hand differed significantly among three groups of the workers divided according to the CEI. These findings suggest that trichloroethylene exposure, even at low levels of less than the short-term exposure limit by the ACGIH, can affect the neuromotor function of workers. The postural instability appears to result from recent exposure, and the increased tremor may occur due to short-term and long-term exposures. Hereafter, such objective measures, along with subjective symptoms, should be carefully used for the occupational exposure limit setting.

International symposium on genotoxic and carcinogenic thresholds

New paradigms for the setting of tolerable exposure limits for carcinogenic chemicals are being discussed world wide, and there is a global discourse in this respect between toxicological science, regulatory bodies and stakeholders (Sweeney et al. 2006; Bader et al. 2007; Bolt and HuiciMontagud 2008). The traditionally accepted general dogma that health-based exposure limits cannot be derived for genotoxic carcinogens has been challenged by new research results (Hengstler et al. 2003). Against this background the Japanese National Institute of Health Science, in conjunction with the Japan Bioassay Research Center convened an international symposium in Tokyo, in order to foster the exchange of ideas between leading Japanese, American and European scientists in this Weld, and at the same time to communicate results of this discussion to Japanese authorities and stakeholders (Fig. 1). The main initiators of the symposium in particular, Shoji Fukushima and Takehiko Nohmi (Kanagawa and Tokyo), favoured a concept to diVerentiate “perfect” and “practical” thresholds for genotoxic compounds, as earlier deWned by Kirsch-Volders et al. (2000) and Hengstler et al. (2003). An analysis of Waddell et al. (2006) was cited comparing published data on GSTP-positive hepatic foci induced by N-nitroso-diethylamine. The foci were observed at doses below the threshold dose for the appearance of tumours. These results suggested that adducts and GSTP-positive foci appear at doses below those at which tumours appear. These results were interpreted to support the observations of the authors that thresholds for carcinogenicity of this genotoxin exist, and that adducts and altered foci appear at lower doses than the threshold for carcinogenicity. Potassium bromate (Kurokawa et al. 1990; Gultekin and Hicyilmaz 2007) and 1,4-dioxane (Stickney et al. 2003; Nannelli et al. 2005; Kuroiwa et al. 2007) were mentioned as examples of compounds with a “perfect threshold”. In total, the symposium covered a methodological spectrum reaching from bacterial mutagenicity assays (Nohmi 2000) up to modern transgenic mouse assays (Nohmi et al. 2000). The main focus of the symposium was on ingredients of food, e.g. heterocyclic amines, nitrosamines or mycotoxins (Huang et al. 2006; Schrickx et al. 2006; Nagashima et al. 2007). A controversial point of discussion was the evaluation of acrylamide detected recently in unexpectedly large amounts in starchy foods that had been cooked at high temperatures (Boettcher et al. 2006). This is biologically converted into the genotoxic epoxide glycidamide (Settels et al. 2008). The scientiWc evaluation of possible threshold mechanisms in this case is a matter of debate, so that mostly linear non-threshold risk extrapolation models are preferred. From the area of food toxicology parallels were drawn to the setting of occupational exposure limits and to concepts favoured by European scientiWc bodies, such as EUROTOX (Foth et al. 2005) and SCOEL (Bolt and Huici-Montagud 2008). The symposium revealed that the implementation of novel toxicological concepts within the regulatory context requires an intensive and well-founded dialogue between scientists, authorities and stakeholders, both on national and international levels. It will now be up to the scientists to further promote this dialogue. Key articles resulting from the symposium will be published in “Genes and Environment”. H. M. Bolt (&) Leibniz Research Centre for Working Environment and Human Factors, Institut fur Arbeitsphysiologie an der Universitat Dortmund, Ardeystr. 67, 44139 Dortmund, Germany e-mail: bolt@ifado.de

Background, approaches and recent trends for setting health-based occupational exposure limits: A minireview

The setting of occupational exposure limits (OELs) are founded in occupational medicine and the predictive toxicological testing, resulting in exposure–response relationships. For compounds where a No-Observed-Adverse-Effect-Level (NOAEL) can be established, health-based OELs are set by dividing the NOAEL of the critical effect by an overall uncertainty factor. Possibly, the approach may also be used for carcinogens if the mechanism is epigenetic or the genetic effect is secondary to effect from reactions with proteins such as topoisomerase inhibitors, and mitotic and meiotic spindle poisons. Additionally, the NOAEL approach may also be used for compounds with weak genotoxic effect, playing no or only a minor role in the development of tumours. No health-based OEL can be set for direct-acting genotoxic compounds where the life-time risks may be estimated from the low-dose linear non-threshold extrapolation, allowing a politically based exposure level to be set. OELs are set by several agencies in the US and Europe, but also in-house in major chemical and pharmaceutical companies. The benchmark dose approach may in the future be used where it has advantage over the NOAEL approach. Also, more attention should be devoted to sensitive groups, toxicological mechanisms and interactions as most workplace exposures are mixtures.

The Challenge of Setting Occupational Exposure Limits (OELs) for Odorants and Irritants

MAB3-PD-02 Introduction: Setting occupational exposure limits (OELs) for odorous or irritating chemicals is a global occupational health challenge. Industrial hygienists and toxicologists are expected to set OELs for the numerous chemicals that are being introduced to the workplace. Often, however, there is inadequate knowledge about the toxicology of these chemicals and, if they are odorous or a sensory irritant, these characteristics are usually not recognized until they are used in large quantities. This paper presents a novel and simple method for setting OELs based on chemosensory models, taking into account odor and irritation thresholds. Methods: The importance of accounting for risk perception and communication, conditioned responses, interindividual variability in tolerance, detection, and susceptibility when identifying an appropriate workplace concentration of odorous or irritant compounds is evaluated according to 3 chemosensory models defined by a chemical's odor and irritation thresholds. These parameters are then incorporated into a flowchart style methodology, which can be used to set an OEL for a specific chemical. Results: Our analysis indicates the OEL identified for a chemical odorant or irritant will depend on the type of chemosensory effect that the chemical is likely to exhibit. Experience has shown that chemicals with a low odor threshold often require low OELs, even though many do not pose toxicity or irritation at those air concentrations. Discussion and Conclusions: There remains a need for OEL-setting organizations around the world to agree upon the percentage of the workforce that an OEL should protect and the types of toxicologic endpoints that are sufficiently important to protect against (eg, transient eye irritation, enzyme induction, or other reversible effects). This is particularly true for the odorants and irritants. In the main, the methods presented here are worthy of consideration in the setting of OELs until better and more thorough consensus among professions is reached. This method could also be extended to environmental regulation where risk perception plays a dominate role in whether the public views the exposure as being reasonable or safe.

Local effects in the respiratory tract: relevance of subjectively measured irritation for setting occupational exposure limits

Chemosensory effects of stimulation by a chemical can either be irritating (trigeminal stimulation) or odorous (olfactory stimulation) or both. For odorous irritants, a clear-cut distinction between odour and irritation is difficult to make. The differences in the lowest concentration found to be irritating to the respiratory tract in humans when compared to experimental animals has brought much debate in the process of setting occupational exposure limits (OELs) for such chemicals. In this paper it will be discussed as to how far subjectively measured sensory irritation threshold levels can be used to establish OELs. Data on respiratory irritation of four odorous irritants were retrieved from public literature and discussed, viz. acetone, formaldehyde, furfural and sulphur dioxide. Objective measures of irritation yielded results that differed from subjective evaluations. Important factors modulating the reported levels of irritation and health symptoms include the perception of odour intensity, exposure history and the individual's bias to report irritation on the basis of his/her prejudice or knowledge of the compound. Subjective measures alone are less appropriate for establishing sensory irritation thresholds of odorous irritants and are, therefore, less suitable to establish OELs without supporting evidence. Objectively measured irritation in humans, the Alarie assay (an experimental animal test assessing the concentration that results in a 50% reduction of the breathing frequency) and repeated exposure studies in animals may be of help to study objective irritation. If subjective measurements are used to study sensory irritation, the study design should at least include: measurement of both incidence and severity determined at several concentrations, an appropriate (0 ppm) control condition, preferably a non-irritant odorant control exposure, validated questionnaires and correct concentration measurements.

Biological monitoring of experimental human exposure to hydrocarbon solvent mixtures

The aim of the study was to develop and to validate a suitable analytical method in order to assess the internal exposure of persons to commercial products of hydrocarbon solvent mixtures (HSM). Twenty healthy volunteers were exposed to vapours of five commercial HSM for 8 h at 200–1000 mg/m 3 air. Aromatic-rich, aromatic-poor and aromatic-free HSM were used, as well as isohexane and technical hexane mixtures. A total of 300 exposures were carried out at rest or with an exercise period of 10 min/h at 50 and 75 W. Blood samples for the determination of the HSM were collected before and immediately after exposure. They were analyzed with a headspace analyzer by gas chromatography and mass spectrometry. The analytical method has detection limits of 2–50 μg HSM/L blood. With this method we obtained intra- and interassay variation coefficients of 3.7–15.1%, at concentrations of 53–1500 μg HSM/L blood. The mean values of the HSM of the 20 volunteers after 8 h range between 89 μg/L (technical hexane-mixture) and 1369 μg/L blood (aromatic-free HSM) at rest. Physical exercises of 50 and 75 W, respectively, lead to a significant increase of the blood-concentrations by mean factors between 1.2 and 1.9 for the five HSM. In conclusion, our results demonstrate that physical activity should be considered in the setting of occupational exposure limits.

The role of odor and irritation, as well as risk perception, in the setting of occupational exposure limits

This paper reviews current research regarding the relationship between odor perception or irritation and setting an occupational exposure limit (OEL). Special focus was directed at those settings where a small fraction of persons report unacceptable responses to concentrations well below the OEL. We evaluated the published literature on the topic of irritation and olfactory response to exposure to industrial chemicals. More than a dozen researchers have been active in this area over the past 10 years. It was found that for some chemicals, even when one maintains airborne concentrations below a particular OEL, this level of exposure may not be adequate to prevent all persons from reporting an appreciable adverse response. In some cases, worker's pre-existing belief systems about the source of an odor may be sufficient to require that they have not be exposed to any detectable concentration. In addition, detection of odors by workers may tap into the person's aversion to odors, in general. In both situations, it is often necessary to address these specific issues through risk communication and dealing directly with risk perception. For practical reasons, the current objective of organizations charged with setting OELs for chemicals is to identify concentrations that do not cause irritation or widespread reports of unpleasant sensory stimulation in the vast majority of workers (e.g., about 80-95%).

Evaluating the human response to chemicals: odor, irritation and non-sensory factors

Although airborne chemicals can directly elicit adverse reactions via stimulation of the olfactory and trigeminal nerves, such as sensory irritation of the mucous membranes of the eyes, nose and throat, an individual's subjective experience is often the result of a complex sequence of events involving those sensory, physiological signals and psychological processes involved in perception, memory and judgment. To evaluate the contribution of these processes, an information-processing model of chemosensory perception is introduced. The model incorporates (1) the perception of odor and trigeminal irritation, and accompanying physiological and somatic changes that follow directly from the encounter with volatile organic compounds (VOCs) in the environment (bottom-up processing), and (2) any physiological/ somatic changes and subjective experiences of irritancy that are influenced by cognitive processes that have been primed by the perception of odor (top-down processing). The model is illustrated with data from our laboratory, and its utility in the context of setting occupational exposure limits is discussed.

Assessing the Health Implications for Healthcare Workers of Regulatory Changes Eliminating Locally Developed Occupational Exposure Limits in Favor of TLVs: An Evidence-based Bipartite Approach

In response to the intention of the Workers' Compensation Board of British Columbia (WCB of BC) to eliminate made-in-BC occupational exposure limits (OELs) and adopt threshold limit values (TLVs), this study assessed the potential health impacts on healthcare workers (HCWs) of the proposed change, by (1) reviewing the processes used to establish the OELs and TLVs, (2) selecting of substances of health concern for HCWs, (3) identifying chemicals with discordances between existing OELs and the 2002 TLVs, and 4) reviewing the discordances and assessing the potential health implications. Differences in philosophies, policies and processes that influenced the setting of OELs and TLVs were substantial. The TLV process involves U.S. and international priorities; in BC, a tripartite committee determined OELs taking into consideration how OELs should be interpreted in the local context. 47 chemicals of concern to BC HCWs were discordant, with significant discordances totalling 57; 15 compounds had BC 8-hour OELs lower than their respective TLVs and three TLVs were lower than the 8-hour BC OELs. Review of six chemicals with discordances suggested a potential for increased risks of adverse health effects. Eliminating the local capacity and authority to set OELs is unlikely to cause major health problems in the short run, but as chemicals in use locally may not have up-to-date TLVs, eliminating the capacity for local considerations should be undertaken with great caution. While the WCB of BC did implement the change, the present report resulted in procedural changes that will provide better protection for the workforce.

Evaluation of current biological exposure index for occupational N, N-dimethylformamide exposure from synthetic leather workers.

The aim of this study was (1) to investigate the correlation between external exposure to N, N-dimethylformamide (DMF) and urinary excretion of DMF and N-methylformamide; (2) to assess whether the correspondence between the current occupational exposure limit setting and recommended urinary biological exposure index is substantial; and (3) to evaluate whether coexposure to toluene, methyl ethyl ketone, and ethyl acetate has an effect on urinary excretion of DMF and N-methylformamide (NMF). Urinary DMF and NMF were significantly correlated (P < 0.01) with one another and also significantly correlated with airborne DMF (P < 0.01) over the range of 1.55 to 152.8 mg/m. Urinary DMF can be considered a complementary marker for short-term exposure. Urinary concentration of NMF and DMF, corresponding to the 8-hour exposure to airborne DMF at 30 mg/m, was estimated to 38.4 mg/L or 39.4 mg/g creatinine for NMF and to 0.92 mg/L or 0.96 mg/g creatinine for DMF.

Sensory and Associated Reactions to Mineral Dusts: Sodium Borate, Calcium Oxide, and Calcium Sulfate

Occupational exposure limits (OELs) for irritant dusts have had no quantifiable bases. This study (1) charted chemosensory feel, denoted chemesthesis here, to dusts of calcium oxide (1 to 5 mg/m3), sodium tetraborate pentahydrate [sodium borate] (5 to 40 mg/m3), and calcium sulfate (10 to 40 mg/m3); (2) examined correlates of the chemesthetic sensations; and (3) sought to illuminate the basis for potency. Twelve screened men exercised against a light load while they breathed air in a dome fed with controlled levels of dust for 20 min. Measured parameters included nasal resistance, nasal secretion, minute ventilation, heart rate, blood oxygenation, mucociliary transport time, and chemesthetic magnitude, calibrated to pungency of carbon dioxide. Subjects registered time-dependent feel from exposures principally in the nose, secondarily in the throat, and hardly in the eyes. Calcium oxide had the greatest potency, followed by sodium borate, with calcium sulfate a distant third. Of the physiological parameters, amount of secretion showed the best association with chemesthetic potency. That measure, as well as mucociliary transport time and minute ventilation, went into calculation of mass of dust dissolved into mucus. The calculations indicated that the two alkaline dusts increased in equal molar amounts with time. At equal molar concentrations, they had, to a first approximation, equal chemesthetic magnitude. On the basis of mass concentration in air or dissolved into mucus, calcium oxide and sodium borate differed in potency by a factor just above five, equal to the difference in their molecular weights. This relationship could inform the setting of OELs for a critical effect of irritation.