Occupational exposure to ethylene oxide. Relation between in vivo dose and exposure dose.

Osterman-Golkar, Siv; Bergmark, Emma

doi:10.5271/sjweh.1906

Cited by 21 publications

(4 citation statements)

References 15 publications

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“…This conclusion is based on the assumption that other mammalian hemoglobin would respond similarly, however, the precise relationships do need to be elucidated. These relationships have been demonstrated in subsequent research (42,43).…”

Section: Hemogloblin Alkylation By Ethylene Oxidementioning

confidence: 62%

Validation of Biological Markers for Quantitative Risk Assessment

Schulte¹,

Mazzuckelli²

1991

Environmental Health Perspectives

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The evaluation of iolgia markers is recoied as necsry to the future oftokcOy , epideniology, and q Iive risk assment. For bio cl nmrkes to becm widely accepted, their validity must be ascertained. This paper explores the range ofconsiderations that compose the concept of validiBt as it applies to the evaluation of bioogical markers. Three broad categories of validity (meaem ent, internal study, and external) are discussed in the context of evWaluating data for use inquantitative risk at. Frticular attention is given to the importnce ofmeuement validity in the consideration ofwhether to use biological markers in epidemiologic studies. The Three broad categories of validity can be distinguished: measurement validity, internal study validity, and external validity. Measurement validity has been defined as an expression ofthe degree to which ".. . a measurement measures what it purports to measure" (9). Internal study validity is the degree to which inferences drawn from a sample are warranted when account is taken of the study methods, the representativeness of the study sample, and the nature ofthe population from which the sample is drawn (9). External study validity is the extent to which the findings of a study can be generalized to other populations (9). likely that the risk assessments constructed from those measurements will also be invalid. Measurement validity characterizes the extent to which a marker ofa phenomenon has content validity (i.e., pertains to the underlying phenomenon); construct validity (i.e., correlates with other relevant characteristics of the underlying phenomenon); and criterion validity (i.e., predicts some component of the underlying phenomenon). In general, these three components ofmeasurement validity are best assessed in terms of the extent or degree to which they apply to the underlying phenomenon, rather than as an all-or-none condition (JO). Content ValidityContent validity is the extent to which a marker "incorporates the domain ofthe phenomenon under study" (9). For example, a marker of internal dose will have content validity if it reflects the dose contributed by all routes of exposure. A marker of effect will have content validity if it encompasses the essential characteristics of the disease it represents. In other words, the marker must pertain to the appropriate target organ, or its relationship to the natural history ofthe disease in question must be unambiguous. For example, a DNA adduct of benzo(a)pyrene (BaP) will have content validity as a marker of exposure in a study ofBaP-induced lung cancer, since the involvement ofDNA in BaP-induced carcinogenesis is well documented. In contrast, the development of DNA adducts in the N7 position might not have content validity as a marker of biologically effective dose ifthe 06 methylguanine adduct is shown to be that which is most clearly related to the carcnogenic process. However, the N7 adducts might be reasonably valid markers ofBaP biologically effective dose ifthe production of06 and N7 adducts are directly proportion...

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Section: Hemogloblin Alkylation By Ethylene Oxidementioning

confidence: 62%

Validation of Biological Markers for Quantitative Risk Assessment

Schulte¹,

Mazzuckelli²

1991

Environmental Health Perspectives

View full text Add to dashboard Cite

show abstract

Section: Hemogloblin Alkylation By Ethylene Oxidementioning

confidence: 62%

Validation of biological markers for quantitative risk assessment.

Schulte

Mazzuckelli

1991

Environ Health Perspect

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The evaluation of biological markers is recognized as necessary to the future of toxicology, epidemiology, and quantitative risk assessment. For biological markers to become widely accepted, their validity must be ascertained. This paper explores the range of considerations that compose the concept of validity as it applies to the evaluation of biological markers. Three broad categories of validity (measurement, internal study, and external) are discussed in the context of evaluating data for use in quantitative risk assessment. Particular attention is given to the importance of measurement validity in the consideration of whether to use biological markers in epidemiologic studies. The concepts developed in this presentation are applied to examples derived from the occupational environment. In the first example, measurement of bromine release as a marker of ethylene dibromide toxicity is shown to be of limited use in constructing an accurate quantitative assessment of the risk of developing cancer as a result of long-term, low-level exposure. This example is compared to data obtained from studies of ethylene oxide, in which hemoglobin alkylation is shown to be a valid marker of both exposure and effect.

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“…The relatively low average EO concentrations that affected the cells in our experiments are representative to the serum levels of occupationally exposed individuals, which largely depends on the actual airborne concentration of EO [Osterman‐Golkar and Bergmark, ]. Brugnone et al [] monitored occupational exposure to EO by measuring the concentrations in the ambient air and blood and found that the EO concentration in the blood was, on average, 3.3 times higher than its concentration in the air.…”

Section: Discussionmentioning

confidence: 84%

Susceptibility of lung epithelial cells to alkylating genotoxic insult

Nagy

Ádány

Szűcs

et al. 2013

Environ and Mol Mutagen

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Alkylation is one of the most common types of DNA damage that can lead to mutations and cancer. Lung is the primary target organ of airborne alkylators such as ethylene oxide (EO). However, the ability of EO to cause lung cancer has not been clearly demonstrated yet. The aim of this study was to investigate the susceptibility of lung cells to alkylating DNA insult by detecting EO-mediated DNA damage with the alkaline comet assay in human lung epithelial cells, peripheral blood lymphocytes, and keratinocytes. The susceptibility of these cell types toward the alkylating insult induced by EO was compared against the oxidative DNA insult induced by hydrogen peroxide (H2 O2 ). Due to the volatility of EO, its active concentrations were monitored by gas chromatography during exposure and were found to decrease significantly in a time-dependent manner. EO induced a statistically significant genotoxic effect at the lowest concentration used (16.4 µM) in lung epithelial cells and in lymphocytes, while in keratinocytes, a genotoxic effect was not detected until 55.5 µM EO. However, lung epithelial cells demonstrated increased resistance to oxidative insult. In fact, oxidative DNA damage detectable by endonuclease treatment was minimal in lung cells compared with the other cell types. These results suggest an increased sensitivity of lung epithelial cells toward the alkylating effects of EO, which was not observed for oxidative DNA damage. Our findings point out the importance of DNA alkylation and the possible role of EO on the induction of lung cancer.

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Occupational exposure to ethylene oxide. Relation between in vivo dose and exposure dose.

Cited by 21 publications

References 15 publications

Validation of Biological Markers for Quantitative Risk Assessment

Validation of Biological Markers for Quantitative Risk Assessment

Validation of biological markers for quantitative risk assessment.

Susceptibility of lung epithelial cells to alkylating genotoxic insult

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