Geruchsintensive Stoffe: Grundlagen, Bewertung und Markierung

Odours from substances at the workplace are often strong, unpleasant and perceptible even at concentrations below the valid MAK values. “Odour-associated symptoms” such as nausea and headaches may develop as a result of a special processing of neurophysiological signals, a specific neuroanatomical connectivity and the evolutionary significance of olfaction. These effects cannot be taken into consideration for the derivation of a MAK value because they occur only in isolated cases. Substances at the workplace that are associated with these kinds of effects are designated in the List of MAK and BAT Values with a corresponding footnote. This article presents the scientific background and the specific procedure used for applying the footnote. By stimulating specialized odour receptors, odours are perceptible even at very low concentrations. After crossing only a few synaptic junctions, the odour information reaches regions of the brain such as the limbic system, the vegetative nuclei of the hypothalamus and the reticular formation. Odours, particularly unpleasant ones, are often perceived as a sign of danger based on individual experiences and evolutionary developments. However, individual responses differ considerably and this variation cannot be explained adequately by physiological mechanisms. Therefore, in order to have the potential of inducing “odour-associated symptoms”, the workplace substances in question must have a low odour threshold and an unpleasant odour quality. The methods used to identify these odour characteristics are quite heterogeneous and have not been standardized. Different sources were used to determine the odour characteristics of the 43 workplace substances from the List of MAK and BAT Values that potentially met these criteria. After the data were checked for plausibility, 23 of the substances were designated with the footnote following a systematic evaluation

In vitro genotoxicity of dibutyl phthalate on A549 lung cells at air-liquid interface in exposure concentrations relevant at workplaces.

The ubiquitous use of phthalates in various materials and the knowledge about their potential adverse effects is of great concern for human health. Several studies have uncovered their role in carcinogenic events and suggest various phthalate-associated adverse health effects that include pulmonary diseases. However, only limited information on pulmonary toxicity is available considering inhalation of phthalates as the route of exposure. While in vitro studies are often based on submerged exposures, this study aimed to expose A549 alveolar epithelial cells at the air-liquid interface (ALI) to unravel the genotoxic and oxidative stress-inducing potential of dibutyl phthalate (DBP) with concentrations relevant at occupational settings. Within this scope, a computer modeling approach calculating alveolar deposition of DBP particles in the human lung was used to define in vitro ALI exposure conditions comparable to potential occupational DBP exposures. The deposited mass of DBP ranged from 0.03 to 20 ng/cm2 , which was comparable to results of a human lung particle deposition model using an 8 h workplace threshold limit value of 580 μg/m3 proposed by the Scientific Committee on Occupational Exposure Limits for the European Union. Comet and Micronucleus assay revealed that DBP induced genotoxicity at DNA and chromosome level in sub-cytotoxic conditions. Since genomic instability was accompanied by increased generation of the lipid peroxidation marker malondialdehyde, oxidative stress might play an important role in phthalate-induced genotoxicity. The results highlight the importance of adapting in vitro studies to exposure scenarios relevant at occupational settings and reconsidering occupational exposure limits for DBP

Construction of an in vitro air–liquid interface exposure system to assess the toxicological impact of gas and particle phase of semi-volatile organic compounds.

Anthropogenic activities and industrialization render continuous human exposure to semi-volatile organic compounds (SVOCs) inevitable. Occupational monitoring and safety implementations consider the inhalation exposure of SVOCs as critically relevant. Due to the inherent properties of SVOCs as gas/particle mixtures, risk assessment strategies should consider particle size-segregated SVOC association and the relevance of released gas phase fractions. We constructed an in vitro air–liquid interface (ALI) exposure system to study the distinct toxic effects of the gas and particle phases of the model SVOC dibutyl phthalate (DBP) in A549 human lung epithelial cells. Cytotoxicity was evaluated and genotoxic effects were measured by the alkaline and enzyme versions of the comet assay. Deposited doses were assessed by model calculations and chemical analysis using liquid chromatography tandem mass spectrometry. The novel ALI exposure system was successfully implemented and revealed the distinct genotoxic effects of the gas and particle phases of DBP. The empirical measurements of cellular deposition and the model calculations of the DBP particle phase were concordant.The model SVOC DBP showed that inferred oxidative DNA damage may be attributed to particle-related effects. While pure gas phase exposure may follow a distinct mechanism of genotoxicity, the contribution of the gas phase to total aerosol was comparably low