Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats

Appelman, L.M.; Woutersen, Ruud; Feron, V.J.; Hooftman, R.N.; Notten, W.R.F.

doi:10.1002/jat.2550060506

Cited by 33 publications

(12 citation statements)

References 10 publications

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“…This is comparable with the NOAEC of 150 ppm found in a subacute repeated dose-study (6 h/day, 5 days/week, 4 weeks) in rats, based on histopathological findings in the OE, in particular loss of microvilli, thinning and disarrangement (Appelman et al 1986), whereas 150 ppm was a LOAEC in a subchronic study (6 h/day, 5 days/week, 13 weeks) in rats based on minimal olfactory degeneration at 150 ppm (NOAEC 50 ppm). Mild inflammation and hyperplasia of the respiratory epithelium started at 500 ppm (Dorman et al 2008).…”

Section: Part 3: Recommendation For the Derivation Of Occupational Exsupporting

confidence: 88%

Sensory irritation as a basis for setting occupational exposure limits

Bartsch²,

et al. 2014

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There is a need of guidance on how local irritancy data should be incorporated into risk assessment procedures, particularly with respect to the derivation of occupational exposure limits (OELs). Therefore, a board of experts from German committees in charge of the derivation of OELs discussed the major challenges of this particular end point for regulatory toxicology. As a result, this overview deals with the question of integrating results of local toxicity at the eyes and the upper respiratory tract (URT). Part 1 describes the morphology and physiology of the relevant target sites, i.e., the outer eye, nasal cavity, and larynx/pharynx in humans. Special emphasis is placed on sensory innervation, species differences between humans and rodents, and possible effects of obnoxious odor in humans. Based on this physiological basis, Part 2 describes a conceptual model for the causation of adverse health effects at these targets that is composed of two pathways. The first, “sensory irritation” pathway is initiated by the interaction of local irritants with receptors of the nervous system (e.g., trigeminal nerve endings) and a downstream cascade of reflexes and defense mechanisms (e.g., eyeblinks, coughing). While the first stages of this pathway are thought to be completely reversible, high or prolonged exposure can lead to neurogenic inflammation and subsequently tissue damage. The second, “tissue irritation” pathway starts with the interaction of the local irritant with the epithelial cell layers of the eyes and the URT. Adaptive changes are the first response on that pathway followed by inflammation and irreversible damages. Regardless of these initial steps, at high concentrations and prolonged exposures, the two pathways converge to the adverse effect of morphologically and biochemically ascertainable changes. Experimental exposure studies with human volunteers provide the empirical basis for effects along the sensory irritation pathway and thus, “sensory NOAEChuman” can be derived. In contrast, inhalation studies with rodents investigate the second pathway that yields an “irritative NOAECanimal.” Usually the data for both pathways is not available and extrapolation across species is necessary. Part 3 comprises an empirical approach for the derivation of a default factor for interspecies differences. Therefore, from those substances under discussion in German scientific and regulatory bodies, 19 substances were identified known to be human irritants with available human and animal data. The evaluation started with three substances: ethyl acrylate, formaldehyde, and methyl methacrylate. For these substances, appropriate chronic animal and a controlled human exposure studies were available. The comparison of the sensory NOAEChuman with the irritative NOAECanimal (chronic) resulted in an interspecies extrapolation factor (iEF) of 3 for extrapolating animal data concerning local sensory irritating effects. The adequacy of this iEF was confirmed by its application to additional substances with lower data density (acet...

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Section: Part 3: Recommendation For the Derivation Of Occupational Exsupporting

confidence: 88%

Sensory irritation as a basis for setting occupational exposure limits

Bartsch²,

et al. 2014

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“…Acetaldehyde was the major contributor to the HI at both sites and is known to cause irritation of the olfactory epithelium at chronic exposure concentrations three times higher than those observed at Hickory and RCSP. 36,37 While the overall HI of samples collected near and remote from UNG wells was similar, the contribution of UNG emissions to the overall HI was 6 times higher near wells (12%) than remote from wells (2%) ( Table S2). At Hickory, UNG emissions accounted for approximately 44% of the total HI excluding OVOCs.…”

Section: ■ Introductionmentioning

confidence: 97%

Impact of Marcellus Shale Natural Gas Development in Southwest Pennsylvania on Volatile Organic Compound Emissions and Regional Air Quality

Swarthout

Russo

Zhou

et al. 2015

Environ. Sci. Technol.

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The Marcellus Shale is the largest natural gas deposit in the U.S. and rapid development of this resource has raised concerns about regional air pollution. A field campaign was conducted in the southwestern Pennsylvania region of the Marcellus Shale to investigate the impact of unconventional natural gas (UNG) production operations on regional air quality. Whole air samples were collected throughout an 8050 km(2) grid surrounding Pittsburgh and analyzed for methane, carbon dioxide, and C1-C10 volatile organic compounds (VOCs). Elevated mixing ratios of methane and C2-C8 alkanes were observed in areas with the highest density of UNG wells. Source apportionment was used to identify characteristic emission ratios for UNG sources, and results indicated that UNG emissions were responsible for the majority of mixing ratios of C2-C8 alkanes, but accounted for a small proportion of alkene and aromatic compounds. The VOC emissions from UNG operations accounted for 17 ± 19% of the regional kinetic hydroxyl radical reactivity of nonbiogenic VOCs suggesting that natural gas emissions may affect compliance with federal ozone standards. A first approximation of methane emissions from the study area of 10.0 ± 5.2 kg s(-1) provides a baseline for determining the efficacy of regulatory emission control efforts.

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“…An acetaldehyde exposure study on rats (0, 150, and 500 ppm, 6 h a day, 5 d a week, for 4 wk) indicated that the NOEL for acetaldehyde in rats is 150 ppm [14][15][16] . Another exposure study on hamsters (390, 1,340, and 4,560 ppm, 6 h a day, 5 d a week, for 90 d) indicated that the NOAEL for acetaldehyde in hamsters is 390 ppm 14) .…”

Section: Discussionmentioning

confidence: 99%

Urinary 8-Hydoxydeoxyguanosine (8-OHdG) and Plasma Malondialdehyde (MDA) Levels in Aldh2 Knock-Out Mice under Acetaldehyde Exposure

et al. 2006

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To clarify the carcinogenicity of acetaldehyde when associated with ALDH (aldehyde dehydrogenase) 2 polymorphism, Aldh2 knock-out (Aldh2-/-) mice and their wild type (Aldh2+/+) mice were exposed to two different concentrations of acetaldehyde (125ppm and 500ppm) for two weeks. Aldh2-/-mice, which have the same genetic background as C57BL/6J (wild mice) except for the Aldh2 gene, were used as models of humans who lack ALDH2 activity. Urinary 8-hydroxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) levels were measured as indicators of oxidative DNA damage and lipid peroxidation, respectively. At 125 ppm acetaldehyde exposure for 12 d, urinary 8-OHdG levels in Aldh2+/+ mice did not increase. However, urinary 8-OHdG levels in Aldh2-/-mice were slightly increased by the end of the exposure. On the other hand, plasma MDA levels did not increase in either Aldh2-/-or Aldh2+/+ mice. At 500 ppm, urinary 8-OHdG levels in both Aldh2-/-and Aldh2+/+ mice significantly increased after 6 and 12 d, but there was no genetic difference. On the other hand, plasma MDA levels in Aldh2+/+ and Aldh2-/-mice did not increase at either 125 ppm or 500 ppm after two weeks of exposure. In conclusion, it is suspected that DNA was damaged by acetaldehyde inhalation, and that susceptibility to acetaldehyde varies according to Aldh2 genotype.

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Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats

Cited by 33 publications

References 10 publications

Sensory irritation as a basis for setting occupational exposure limits

Sensory irritation as a basis for setting occupational exposure limits

Impact of Marcellus Shale Natural Gas Development in Southwest Pennsylvania on Volatile Organic Compound Emissions and Regional Air Quality

Urinary 8-Hydoxydeoxyguanosine (8-OHdG) and Plasma Malondialdehyde (MDA) Levels in Aldh2 Knock-Out Mice under Acetaldehyde Exposure

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