Dataset Information

A short-term inhalation study to assess the reversibility of sensory irritation in human volunteers.

ABSTRACT: Sensory irritation is an acute adverse effect caused by chemicals that stimulate chemoreceptors of the upper respiratory tract or the mucous membranes of the outer eye. The avoidance of this end point is of uttermost importance in regulatory toxicology. In this study, repeated exposures to ethyl acrylate were analyzed to investigate possible carryover effects from day to day for different markers of sensory irritation. Thirty healthy subjects were exposed for 4 h on five subsequent days to ethyl acrylate at concentrations permitted by the German occupational exposure limit at the time of study. Ratings of eye irritation as well as eye blinking frequencies indicate the elicitation of sensory irritation. These markers of sensory irritation showed a distinct time course on every single day. However, cumulative carryover effects could not be identified across the week for any marker. The rhinological and biochemical markers could not reveal hints for more pronounced sensory irritation. Neither increased markers of neurogenic inflammation nor markers of immune response could be identified. Furthermore, the performance on neurobehavioral tests was not affected by ethyl acrylate and despite the strong odor of ethyl acrylate the participants improved their performances from day to day. While the affected physiological marker, the increased eye blinking frequency stays roughly on the same level across the week, subjective markers like perception of eye irritation decrease slightly from day to day though the temporal pattern of, i.e., eye irritation perception stays the same on each day. A hypothetical model of eye irritation time course derived from PK/PD modeling of the rabbit eye could explain the within-day time course of eye irritation ratings repeatedly found in this study more precisely.

SUBMITTER: Kleinbeck S

PROVIDER: S-EPMC7261732 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A short-term inhalation study to assess the reversibility of sensory irritation in human volunteers.

Kleinbeck Stefan S Schäper Michael M Pacharra Marlene M Lehmann Marie Louise ML Golka Klaus K Blaszkewicz Meinolf M Brüning Thomas T van Thriel Christoph C

Archives of toxicology 20200317 5

Sensory irritation is an acute adverse effect caused by chemicals that stimulate chemoreceptors of the upper respiratory tract or the mucous membranes of the outer eye. The avoidance of this end point is of uttermost importance in regulatory toxicology. In this study, repeated exposures to ethyl acrylate were analyzed to investigate possible carryover effects from day to day for different markers of sensory irritation. Thirty healthy subjects were exposed for 4 h on five subsequent days to ethyl ...[more]

PMID: 32185413

Similar Datasets

Project description:BACKGROUND: A standard short-term inhalation study (STIS) was applied for hazard assessment of 13 metal oxide nanomaterials and micron-scale zinc oxide. METHODS: Rats were exposed to test material aerosols (ranging from 0.5 to 50 mg/m3) for five consecutive days with 14- or 21-day post-exposure observation. Bronchoalveolar lavage fluid (BALF) and histopathological sections of the entire respiratory tract were examined. Pulmonary deposition and clearance and test material translocation into extra-pulmonary organs were assessed. RESULTS: Inhaled nanomaterials were found in the lung, in alveolar macrophages, and in the draining lymph nodes. Polyacrylate-coated silica was also found in the spleen, and both zinc oxides elicited olfactory epithelium necrosis. None of the other nanomaterials was recorded in extra-pulmonary organs. Eight nanomaterials did not elicit pulmonary effects, and their no observed adverse effect concentrations (NOAECs) were at least 10 mg/m3. Five materials (coated nano-TiO2, both ZnO, both CeO2) evoked concentration-dependent transient pulmonary inflammation. Most effects were at least partially reversible during the post-exposure period.Based on the NOAECs that were derived from quantitative parameters, with BALF polymorphonuclear (PMN) neutrophil counts and total protein concentration being most sensitive, or from the severity of histopathological findings, the materials were ranked by increasing toxic potency into 3 grades: lower toxic potency: BaSO4; SiO2.acrylate (by local NOAEC); SiO2.PEG; SiO2.phosphate; SiO2.amino; nano-ZrO2; ZrO2.TODA; ZrO2.acrylate; medium toxic potency: SiO2.naked; higher toxic potency: coated nano-TiO2; nano-CeO2; Al-doped nano-CeO2; micron-scale ZnO; coated nano-ZnO (and SiO2.acrylate by systemic no observed effect concentration (NOEC)). CONCLUSION: The STIS revealed the type of effects of 13 nanomaterials, and micron-scale ZnO, information on their toxic potency, and the location and reversibility of effects. Assessment of lung burden and material translocation provided preliminary biokinetic information. Based upon the study results, the STIS protocol was re-assessed and preliminary suggestions regarding the grouping of nanomaterials for safety assessment were spelled out.

Project description:Background Most threshold limit values are based on animal experiments. Often, the question remains whether these data reflect the situation in humans. As part of a series of investigations in our exposure lab, this study investigates whether the results on the inflammatory effects of particles that have been demonstrated in animal models can be confirmed in acute inhalation studies in humans. Such studies have not been conducted so far for barium sulfate particles (BaSO4), a substance with very low solubility and without known substance-specific toxicity. Previous inhalation studies with zinc oxide (ZnO), which has a substance-specific toxicity, have shown local and systemic inflammatory respones. The design of these human ZnO inhalation studies was adopted for BaSO4 to compare the effects of particles with known inflammatory activity and supposedly inert particles. For further comparison, in vitro investigations on inflammatory processes were carried out. Methods Sixteen healthy volunteers were exposed to filtered air and BaSO4 particles (4.0 mg/m3) for two hours including one hour of ergometric cycling at moderate workload. Effect parameters were clinical signs, body temperature, and inflammatory markers in blood and induced sputum. In addition, particle-induced in vitro-chemotaxis of BaSO4 was investigated with regard to mode of action and differences between in vivo and in vitro effects. Results No local or systemic clinical signs were observed after acute BaSO4 inhalation and, in contrast to our previous human exposure studies with ZnO, no elevated values of biomarkers of inflammation were measured after the challenge. The in vitro chemotaxis induced by BaSO4 particles was minimal and 15-fold lower compared to ZnO. Conclusion The results of this study indicate that BaSO4 as a representative of granular biopersistent particles without specific toxicity does not induce inflammatory effects in humans after acute inhalation. Moreover, the in vitro data fit in with these in vivo results. Despite the careful and complex investigations, limitations must be admitted because the number of local effect parameters were limited and chronic toxicity could not be studied. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-022-02021-y.

Project description:Purpose This study sought to identify the changes and potential association between sleep characteristics and short-term memory, and mood states among volunteers at different altitudes and times. Method A total of 26 healthy volunteers were recruited from the PLA General Hospital, and we conducted a longitudinal prospective survey for over 1 year from November 2019 to April 2021. First, we collected demographic data, sleep parameters by overnight polysomnography (PSG), short-term memory by digit span test, and mood states by completing a questionnaire with a brief profile of mood states among participants in the plain (53 m). Then, we continuously followed them up to collect data in the 3rd month at an altitude of 1,650 m (on the 3rd month of the 1-year survey period), the 3rd month at an altitude of 4,000 m (on the 6th month of the 1-year survey period), and the 9th month at an altitude of 4,000 m (on the 12th month of the 1-year survey period). Multiple linear regression analysis was used to construct models between sleep parameters and short-term memory, and mood states. Results The prevalence of sleep apnea syndrome (SAS) significantly increased with rising elevation (P < 0.01). The apnea-hypopnea index (AHI), the mean apnea time (MAT), the longest apnea time (LAT), and the duration of time with SaO2 < 90% (TSA90) were increased (P < 0.05), and the mean pulse oxygen saturation (MSpO2), the lowest pulse oxygen saturation (LSpO2), and heart rate were significantly decreased with increasing altitude (P < 0.05). Digit span scores were decreased with increasing altitude (P < 0.001). A negative mood was more severe and a positive mood increasingly faded with rising elevation (P < 0.001). Additionally, linear correlation analysis showed that higher AHI, LAT, and MAT were strongly associated with a greater decline in short-term memory (in the 3rd and 9th month at an altitude of 4,000 m, respectively: rs = −0.897, −0.901; rs = −0.691, −0.749; rs = −0.732, −0.794, P < 0.001), and also were strongly associated with more severe negative mood (in the 3rd month at altitudes of 1,650 m and 4,000 m, respectively: rs = 0.655, 0.715, 0.724; rs = 0.771, 0.638, 0.737, P < 0.000625). Multiple linear regression pointed out that AHI was a significant predictor of negative mood among people at different altitudes (in the 3rd month at an altitude of 1,650 m: TMD = 33.161 + 6.495*AHI; in the 3rd month at an altitude of 4,000 m: TMD = 74.247 + 1.589*AHI, P < 0.05). Conclusion SAS developed easily in high altitudes, most often in CSA (central sleep apnea, CSA). The sleep, short-term memory, and negative mood were significantly more damaged with elevation in volunteers. Sleep parameters were closely associated with short-term memory and mood states in volunteers at high altitudes; the higher the sleep parameters (AHI, LAT, and MAT) scores, the more significant the mood disorders and the more obvious impairment of short-term memory. AHI was a critical predictor of the negative mood of volunteers at different altitudes. This study provides evidence that could help with the prevention and control of sleep disorder, cognitive disorder, and negative mood among populations with high altitudes.

Dataset Information

A short-term inhalation study to assess the reversibility of sensory irritation in human volunteers.

Publications

A short-term inhalation study to assess the reversibility of sensory irritation in human volunteers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets