Derivation of an occupational exposure limit for benzene using epidemiological study quality assessment tools

Schnatter, A. Robert; Rooseboom, Martijn; Kocabaş, Neslihan Aygün; North, Colin M.; Dalzell, Abigail; Twisk, Johannes; Faulhammer, Frank; Rushton, Erik K.; Boogaard, Peter J.; Ostapenkaite, Viktorija; Williams, Stephen D.

doi:10.1016/j.toxlet.2020.05.036

Cited by 10 publications

(5 citation statements)

References 130 publications

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“…Since 2001, the ACGIH ( ACGIH, 2001 ) has recommended a BEI for SPMA of 25 μg/g creatinine (12 μmol/mol creatinine) as a biomonitoring equivalent of exposure to 0.5 ppm benzene in air. In non-smokers, an air benzene level of 0.2 mg/m 3 (0.06 ppm) corresponds to 3 µg SPMA/g creatinine (1.4 μmol/mol) ( Schnatter et al, 2020 ). In 2018, the ECHA Committee for Risk Assessment published an opinion on benzene, recommending a BLV of 2 µg SPMA/g creatinine (0.9 μmol/mol creatinine, equivalent to 0.16 mg/m 3 benzene in air) and in response to recent health concerns, the Committee for Risk Assessment (RAC) has recommended lowering the occupational exposure limit (OEL) to 0.05 ppm benzene in air based on chromosomal damage in bone marrow ( Fustinoni et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

“…In 2018, the ECHA Committee for Risk Assessment published an opinion on benzene, recommending a BLV of 2 µg SPMA/g creatinine (0.9 μmol/mol creatinine, equivalent to 0.16 mg/m 3 benzene in air) and in response to recent health concerns, the Committee for Risk Assessment (RAC) has recommended lowering the occupational exposure limit (OEL) to 0.05 ppm benzene in air based on chromosomal damage in bone marrow ( Fustinoni et al, 2010 ). Meanwhile, following a comprehensive review of toxicology data, Schnatter et al , proposed an OEL of 0.25 ppm (8 h TWA) and derived NOAEL (0.5 ppm) and LOAEL (2 ppm) ( Schnatter et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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Biological Monitoring: Evidence for Reductions in Occupational Exposure and Risk

et al. 2022

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Aims: The aim of this publication is to explore occupational exposure trends from biological monitoring data collected over a period of more than 20 years. The data is stored within the HSE database, which holds more than 950,000 results from 120,000 workers in 8,000 companies. The data were collated for all biological monitoring results for lead, mercury, benzene, and hexamethylene diisocyanate exposures where there have been some regulatory drivers within the reported time period of the data searched.Methods: Relevant results from sample analysed were extracted from the database and categorised by year from 1996 to the end of 2019 for individual blood lead results and individual urine results for mercury, benzene, and hexamethylene diisocyanate. Results were classed by broad occupational sector where possible. Data were reported graphically by analytical biomarker result (as 90th percentile (P90)) and number of samples per year as well as with overall summary statistics. To look at longer-term trends, results were also evaluated as P90 over 6-year periods.Results: In the period 1996–2019, 37,474 blood lead, 11,723 urinary mercury, 9,188 urinary S-phenylmercapturic acid (SPMA, benzene metabolite) and 21,955 urinary hexamethylene diamine (HDA, metabolite of hexamethylene diisocyanate, HDI) samples were analysed and reported. Over the time period the blood lead concentrations saw the P90 reduce from 53 μg/dl 1996) to 24 μg/dl in 2019; the P90 urinary mercury levels reduced from 13.7 μmol/mol creatinine to 2.1 μmol/mol creatinine and the P90 urinary SPMA levels reduced from 133.7 μmol/mol creatinine to 1.7 μmol/mol creatinine. For HDI the P90 results reduced from 2 µmol HDA/mol creatinine in 1996–2000 to 0.7 in 2005–2010 but levels have since increased to 1.0 µmol HDA/mol creatinine (2016–2019).Conclusion: There is strong evidence of reductions in exposure of GB workers to lead, benzene and mercury from the data presented here. These reductions may reflect the impact of national, regional and global regulatory action to reduce exposures however, the loss of high exposure industries (from either GB as a whole or just this dataset i.e., samples are being sent elsewhere) and the increase in automation or substitution also need to be considered as potential factors. The results for HDI show that whilst interventions can reduce exposures significantly, such initiatives may need to be refreshed at intervals to maintain the reductions in exposure. We have observed that exposures move between sectors over time. Waste and recycling (lead, mercury) and tunnelling through contaminated land (benzene) were sectors or tasks associated with significant exposures and may be increasingly areas of concern.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Biological Monitoring: Evidence for Reductions in Occupational Exposure and Risk

et al. 2022

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“…The lack of a p53 response may have been due to the fact that the exposures (reportedly from <1 to 75 ppm benzene) in the McHale et al study were insufficient to induce genotoxicity. This reason can be rejected because the same cohort of workers do show benzene exposure-related increases in aneuploidy (Zhang et al, 2011), and our own literature evaluation suggested genotoxic effects are observable in workers exposed to ≥ 2 ppm benzene (Schnatter et al, 2020). Alternatively, if genotoxicity was present only at the highest exposures it may not have been identified as an exposure-response effect (which would have required a monotonic change in two or more exposure groups).…”

Section: Genetic Toxicity May Follow Hematotoxicity In Humans Formentioning

confidence: 99%

“…Benzene exposure is associated with altered immune status. Occupational exposure to benzene in excess of 2 ppm has been reported to cause significant decreases in white blood cell counts (Kraus et al, 2018; when applying the urine biomonitoring correlation from Lan et al, 2004;Qu et al, 2003;Schnatter et al, 2020). In and of itself white blood cell count can fluctuate substantially without adverse health effect, but when severe cytopenias occur (which can occur with high, long term benzene exposures Aksoy et al, 1972) immune suppression can result, which in turn may increase risk of AML (Gale and Opelz, 2012).…”

Section: Altered Immune Functionmentioning

confidence: 99%

Modes of action considerations in threshold expectations for health effects of benzene

North

Rooseboom

Kocabaş³

et al. 2020

Toxicology Letters

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Understanding the Mode of Action (MOA) for a chemical can help guide decisions in development of Occupational Exposure Limits (OELs). Where sufficient information exists, it can provide the OEL developer the basis for selecting either a health-based or risk-based approach.To support the development of an OEL for benzene, scientific information relevant to MOA assessment for risk-based and health-based OEL approaches was reviewed. Direct-acting mutagenicity was considered as a basis for a risk-based OEL, versus MOAs consistent with a health-based approach: indirect mutagenicity via topoisomerase II inhibition, indirect mutagenicity via reactive oxygen species generation, or an immune-based bone marrow dysfunction. Based on the evidence against direct DNA reactivity, threshold expectations for remaining MOAs, and evidence for dose rate affecting acute myeloid leukemia and myelodysplastic syndrome risk, the weight of evidence favors a health-based OEL approach. In the case of benzene, development of an OEL based on observations of earlier key events (i.e., hematologic changes and genetic toxicity) is anticipated to provide protection from later adverse outcomes such as leukemia.

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“…North et al conducted an exhaustive literature review and evaluated the molecular modes of action (MoA) in benzene-driven pathologies (6). These data led to a MoA-based threshold proposal of 0.25 ppm (8 h-TWA) which the authors consider to be associated with no significant residual cancer risk and also avoiding other adverse effects (7).…”

Section: Introductionmentioning

confidence: 99%

Accurate low-dose exposure assessment of benzene and monoaromatic compounds by diffusive sampling: sampling and analytical method validation according to ISO 23320 for radiello® samplers packed with activated charcoal

Zaratin,

Boaretto,

Schianca

et al. 2023

Front. Public Health

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The research study aimed at providing an accurate low-dose benzene exposure assessment method, by validating diffusive monitoring techniques for benzene personal exposure measurements at workplaces where benzene concentrations are expected in the low ppb range, such as in the present-day chemical, petrochemical, foundry, and pharmaceutical industry. The project was aimed at addressing the need for a robust and fully validated method to perform personal exposure measurements considering that the occupational exposure limit value for benzene is going to be significantly lowered in the next few years. Diffusive sampling offers a reliable alternative to pumped sampling methods, intrinsic safety in potentially explosive atmospheres, lightness, and ease of use. In this study, the radiello® diffusive sampler, with the packed activated charcoal RAD130 adsorbing substrate [suitable for solvent desorption and analysis by high-resolution gas chromatography-flame ionization detection (HRGC-FID)], was used. The experiments have been conducted following the ISO 23320 standard in the range from 0.005 to 0.1 ppm (16 to 320 μg/m3), yielding a full validation of the sampling and analytical method. The sampler performances have fulfilled all requisites of the ISO 23320 standard, in particular: bias due to the selection of a non-ideal sorbent is lower than 10% (no significant back diffusion of benzene due to concentration change in the atmosphere); bias due to storage of samples for up to 2 months is lower than 10%; nominal uptake rate for benzene on RAD130 is 74.65 mL/min; and expanded uncertainty of the sampling and analytical method is 20.6%. The sampling and analytical method is therefore fit-for-purpose for the personal exposure measurements aimed at testing compliance with occupational exposure limit values for benzene. The method is also fit for short-duration exposure monitoring related to specific tasks, and other volatile organic compounds, usually found in the same workplaces, such as aliphatic and aromatic hydrocarbons and some oxygenated compounds, have also been studied. In particular, n-hexane and isopropyl benzene, whose classification is currently under revision, can be efficiently monitored by this technique.

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Derivation of an occupational exposure limit for benzene using epidemiological study quality assessment tools

Cited by 10 publications

References 130 publications

Biological Monitoring: Evidence for Reductions in Occupational Exposure and Risk

Biological Monitoring: Evidence for Reductions in Occupational Exposure and Risk

Modes of action considerations in threshold expectations for health effects of benzene

Accurate low-dose exposure assessment of benzene and monoaromatic compounds by diffusive sampling: sampling and analytical method validation according to ISO 23320 for radiello® samplers packed with activated charcoal

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