Confine and differentiation of irritating and annoying effects of hazardous substances

Status:

completed 11/2010

Aims:

1) provision of substance-related data for description and evaluation of local irritants
2) prevention of cognitive effects in consequence of the chemosensory perception of local irritants

Activities/Methods:

1) Over the past three years, five experimental exposure studies on different chemical agents - acetaldehyde, ethyl acrylate, hydrogen sulfide, methyl methacrylate, and 2-ethylhexanol were conducted. Furthermore, in two psychophysical experiments (a) alternative procedures for assessing odour and nasal irritation thresholds for highly volatile working substances were developed, and (b) different physiological readouts (parameters of breathing, electrodermal activity (EDA)) were tested in experimental olfactometric screenings to derive more objective irritant and olfactory effects from screening experiments.

2) The modulators age and ability to smell were varied systematically investigating methyl methacrylate (MMA) and 2-ethylhexanol (2-EH) in order to analyse group-related differences in dose-effect relationships for different irritants.

Results:

1) The irritant acetaldehyde did not show any adverse effect up to the current MAK-value of 50 ppm. However, the design (5 conditions, 3 hours of post-experimental observation) allowed for derivation of a NOEAC (No Observed Adverse Effect Concentration) or LOAEC (Lowest Observed Adverse Effect Concentration) based on studies in human and for modelling a benchmarkdose approach. The investigation of ethyl acrylate revealed converging hints of adverse effects at the current MAK-value concerning the three investigated effect levels (sensation, behaviour, and physiology). Exposure peaks producing varying effective concentrations at the target organs (chemosensory receptors of nose and eyes) aggravated subjective sensations and the physiological marker blink frequency considerably. These results support our hypothesis of high potential for sensory irritation in ethyl acrylate, which was derived from static olfactometry. Thus, this substance is a model for the rationale of the research project.

2) While MMA at the concentration of MAK-value triggered only weak effects that were incapable of physiological measurement, blink frequency was increased significantly at 20 ppm of 2-EH. This concentration-dependent effect of irritation was not modulated by the age of the subjects. At present, only limited generalizations of these findings are possible. Further studies should review the result. The study using hydrogen sulfide (H₂S) did not demonstrate interference on the secondary level – for the UA III of AGS however, these results were important to determine the OEL for H₂S.

Conclusion: In principle, the newly developed and refined screening methods are capable of generating basic information on irritants; however, the cost-benefit ratio is unfavourable in some cases. The simple and cost-efficient method of using glass vessels for stimulus delivery is sufficient to measure quality assured odour and nasal irritation thresholds for many irritants. Whether the procedure with gas-tight Tedlar® bags is advisable to measure chemosensory thresholds for working substances with (a) low or (b) high boiling points, has to be decided individually for each substance. The investigated parameters of breathing and EDA provided evidence for valid concentrationdependent changes investigating the model substance mercaptoethanol. But these biosignals are prone to artifacts; so screening is demanding with respect to workforce and time in conducting and analysing. These operating expenses can only be reduced by improvement in technical equipment. After that, these effect markers seem to be reasonable for measuring leading indicators of health-based effects depending on concentration. This research project again emphasizes the method of experimental exposures to be the gold standard for investigating chemosensory effects in human. Only this paradigm that is close to reality allows odour and nasal irritation effects to be assessed in a sophisticated manner, to be evaluated qualitatively, and furthermore, dose-effect relationships to be quantified.

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