Abstract
Occupational exposure limits (OELs) are derived for protection from health hazards, assuming that exposed subjects are healthy adult workers. Whether differences in susceptibility to sensory irritation effects from airborne chemicals have to be taken into account is currently under discussion. Thus, we chose atopics as a healthy but possibly susceptible subpopulation that can be identified with a clinical test. To investigate the influence of sex or atopy on sensitivity to airborne chemicals, 22 subjects were exposed for 4 h to ethyl acrylate at three concentrations: 0.05 ppm (odor threshold; sham), 5 ppm (constant), and varying exposure between 0 and 10 ppm. Odor intensity decreased and eye irritation ratings increased in a dose-dependent manner, reflecting the time course of the exposure scenarios. The reports of moderate-to-strong eye irritation were verified by significant increases in eye blink frequency. Our results show that women reported subjective eye irritation to an increasing degree. However, these sex-related differences in ratings could not be verified by objective assessment of eye blink frequency. Atopic subjects reported higher odor intensity than non-atopic subjects, but only during the sham (odorous but not irritating) exposure condition. Differences in ratings on annoyance, and eye or nose irritation were not found. Furthermore, the study revealed that atopic subjects might belong to a group of subjects with frequent eye blink activity. Although the relative increase in blink rates was more pronounced in non-atopic subjects, atopic subjects had significant higher blink rates at the end of the exposure to varying ethyl acrylate concentrations. Our results do not support that atopy enhances chemosensory effects if only the increase of blink rates and not the absolute height are considered as adverse effect. Nevertheless, the results indicate that individuals with frequent eye blink activity should be distinguished from those with normal eye blink activity while investigating blink rates as objective parameter of eye irritation.
Similar content being viewed by others
Notes
We are in this report first and foremost interested in effects linked to biological processes rather than gender identity and/or societal factors. We are, therefore, using the term “sex,” a term commonly used when referring to potential differences between men and women based on the underlying biology, rather than “gender,” a term commonly used when referring to sexual (gender) identity.
References
Acosta MC, Luna C, Quirce S, Belmonte C, Gallar J (2013) Changes in sensory activity of ocular surface sensory nerves during allergic keratoconjunctivitis. Pain 154(11):2353–2362. https://doi.org/10.1016/j.pain.2013.07.012
Andersson L, Bende M, Millqvist E, Nordin S (2009) Attention bias and sensitization in chemical sensitivity. J Psychosom Res 66(5):407–416. https://doi.org/10.1016/j.jpsychores.2008.11.005
Andersson L, Lundberg C, Aström J, Nordin S (2011) Chemosensory attention, habituation and detection in women and men. Int J Psychophysiol 79(2):316–322. https://doi.org/10.1016/j.ijpsycho.2010.11.008
Andersson L, Claeson AS, Ledin L, Wisting F, Nordin S (2013) The influence of health-risk perception and distress on reactions to low-level chemical exposure. Front Psychol 4:816. https://doi.org/10.3389/fpsyg.2013.00816
Bailer J, Witthöft M, Rist F (2006) The Chemical Odor Sensitivity Scale: reliability and validity of a screening instrument for idiopathic environmental intolerance. J Psychosom Res 61(1):71–79. https://doi.org/10.1016/j.jpsychores.2005.11.005
Bengtsson S, Berglund H, Gulyas B, Cohen E, Savic I (2001) Brain activation during odor perception in males and females. NeuroReport 12(9):2027–2033
Bentivoglio AR, Bressman SB, Cassetta E, Carretta D, Tonali P, Albanese A (1997) Analysis of blink rate patterns in normal subjects. Mov Disord 12(6):1028–1034. https://doi.org/10.1002/mds.870120629
Brüning T, Bartsch R, Bolt HM, Desel H, Drexler H, Gundert-Remy U, Hartwig A, Jäckh R, Leibold E, Pallapies D, Rettenmeier AW, Schlüter G, Stropp G, Sucker K, Triebig G, Westphal G, van Thriel C (2014) Sensory irritation as a basis for setting occupational exposure limits. Arch Toxicol 88(10):1855–1879. https://doi.org/10.1007/s00204-014-1346-z
Claeson AS, Andersson L (2017) Symptoms from masked acrolein exposure suggest altered trigeminal reactivity in chemical intolerance. Neurotoxicology 60:92–98. https://doi.org/10.1016/j.neuro.2017.03.007
Claeson AS, Nordin S (2011) Gender differences in nasal chemesthesis: a study of detection and perceived intensity. Chem Percept 4:25–31. https://doi.org/10.1007/s12078-011-9084-6
Claeson AS, Palmquist E, Lind N, Nordin S (2016) Symptom-trigger factors other than allergens in asthma and allergy. Int J Environ Health Res 26(4):448–457. https://doi.org/10.1080/09603123.2015.1135314
Cortese BM, Schumann AY, Howell AN, McConnell PA, Yang QX, Uhde TW (2018) Preliminary evidence for differential olfactory and trigeminal processing in combat veterans with and without PTSD. Neuroimage Clin 17:378–387. https://doi.org/10.1016/j.nicl.2017.09.018
Cruz AA, Garcia DM, Pinto SP (2011) Spontaneous eyeblink activity. Ocul Surf 9(1):29–41. https://doi.org/10.1016/S1542-0124(11)70007-6
Dai YJ, Zhang X, Yang Y, Nan HY, Yu Y, Sun Q, Yan LF, Hu B, Zhang J, Qiu ZY, Gao Y, Cui GB, Chen BL, Wang W (2018) Gender differences in functional connectivities between insular subdivisions and selective pain-related brain structures. J Headache Pain 19(1):24. https://doi.org/10.1186/s10194-018-0849-z
Dalton P (2001) Evaluating the human response to sensory irritation: implications for setting occupational exposure limits. AIHAJ 62(6):723–729. https://doi.org/10.1080/15298660108984681
Dalton P (2003) Upper airway irritation, odor perception and health risk due to airborne chemicals. Toxicol Lett 140–141:239–248. https://doi.org/10.1016/S0378-4274(02)00510-6
DFG (2007) MAK value documentation ethyl acrylate
DFG (2012) MAK value documentation 2-ethylhexanol
Doty RL, Cometto-Muniz JE, Jalowayski AA, Dalton P, Kendal-Reed M, Hodgson M (2004) Assessment of upper respiratory tract and ocular irritative effects of volatile chemicals in humans. Crit Rev Toxicol 34(2):85–142. https://doi.org/10.1080/10408440490269586
Doughty MJ, Naase T (2006) Further analysis of the human spontaneous eye blink rate by a cluster analysis-based approach to categorize individuals with ‘normal’ versus ‘frequent’ eye blink activity. Eye Contact Lens 32(6):294–299. https://doi.org/10.1097/01.icl.0000224359.32709.4d
Doughty MJ, Naase T, Button NF (2009) Frequent spontaneous eyeblink activity associated with reduced conjunctival surface (trigeminal nerve) tactile sensitivity. Graefes Arch Clin Exp Ophthalmol 247(7):939–946. https://doi.org/10.1007/s00417-008-1028-8
Emmen HH, Muijser H, Arts JH, Prinsen MK (2003) Human volunteer study with PGME: eye irritation during vapour exposure. Toxicol Lett 140–141:249–259. https://doi.org/10.1016/S0378-4274(03)00021-3
Green BG, Dalton P, Cowart B, Shaffer G, Rankin K, Higgins J (1996) Evaluating the ‘Labeled Magnitude Scale’ for measuring sensations of taste and smell. Chem Senses 21(3):323–334. https://doi.org/10.1093/chemse/21.3.323
Haftenberger M, Laußmann D, Ellert U, Kalcklösch M, Langen U, Schlaud M, Schmitz R, Thamm M (2013) Prevalence of sensitisation to aeroallergens and food allergens. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 56:687–697
Haumann K, Kiesswetter E, van Thriel C, Blaszkewicz M, Golka K, Seeber A (2003) Breathing and heart rate during experimental solvent exposure of young adults with self-reported multiple chemical sensitivity (sMCS). Neurotoxicology 24(2):179–186. https://doi.org/10.1016/S0161-813X(02)00213-9
Hoffmeyer F, Sucker K, Berresheim H, Monsé C, Jettkant B, Beine A, Raulf M, Bünger J, Brüning T (2017) Impact of internal and external factors on EBC-pH and FeNO changes in humans following challenge with ethyl acrylate. Adv Exp Med Biol 1020:7–16. https://doi.org/10.1007/5584_2017_1
Hoffmeyer F, Sucker K, Berresheim H, Monsé C, Jettkant B, Beine A, Raulf M, Brüning T, Bünger J (2019) Methodological implications and repeatability of nasal nitric oxide: relevance for challenge studies. Adv Exp Med Biol. 1113:1–10. https://doi.org/10.1007/5584_2018_166
Hughes A, Hirsch C, Chalder T, Moss-Morris R (2016) Attentional and interpretive bias towards illness-related information in chronic fatigue syndrome: a systematic review. Br J Health Psychol 21(4):741–763. https://doi.org/10.1111/bjhp.12207
Hughes AM, Chalder T, Hirsch CR, Moss-Morris R (2017) An attention and interpretation bias for illness-specific information in chronic fatigue syndrome. Psychol Med 47(5):853–865. https://doi.org/10.1017/S0033291716002890
Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G (1997) ‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 22(1):39–52. https://doi.org/10.1093/chemse/22.1.39
Johansson SGO, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, Motala C, Ortega Martell JA, Platts-Mills TAE, Ring J, Thien F, Van Cauwenberge P (2004) Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol 113(5):832–836. https://doi.org/10.1016/j.jaci.2003.12.591
Johansson MK, Johanson G, Öberg M (2012) How are asthmatics included in the derivation of guideline values for emergency planning and response? Regul Toxicol Pharmacol 63(3):461–470. https://doi.org/10.1016/j.yrtph.2012.05.010
Johansson MK, Johanson G, Öberg M (2016) Evaluation of the experimental basis for assessment factors to protect individuals with asthma from health effects during short-term exposure to airborne chemicals. Crit Rev Toxicol 46(3):241–260. https://doi.org/10.3109/10408444.2015.1092498
Kleinbeck S, Schäper M, Zimmermann A, Blaszkewicz M, Brüning T, van Thriel C (2017) Prediction of human sensory irritation due to ethyl acrylate: the appropriateness of time-weighted average concentration × time models for varying concentrations. Arch Toxicol 91(9):3051–3064. https://doi.org/10.1007/s00204-017-1934-9
Kleinbeck S, Pacharra M, Schäper M, Blaszkewicz M, Golka K, Brüning T, van Thriel (2018) Sensorische Irritationen durch Ameisensäure: Reagieren allergische Probanden stärker auf kontrollierte Expositionen? (Sensory irritations due to formic acid: Do allergic subjects react more strongly to controlled exposures?) In: Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin e.V. (Hrsg.): Dokumentation der 58. Jahrestagung der DGAUM, 7.-9. März 2018 in München, p 50
Koch K, Pauly K, Kellermann T, Seiferth NY, Reske M, Backes V, Stöcker T, Shah NJ, Amunts K, Kircher T, Schneider F, Habel U (2007) Gender differences in the cognitive control of emotion: an fMRI study. Neuropsychologia 45(12):2744–2754. https://doi.org/10.1016/j.neuropsychologia.2007.04.012
Lang I, Bruckner T, Triebig G (2008) Formaldehyde and chemosensory irritation in humans: a controlled human exposure study. Regul Toxicol Pharmacol 50(1):23–36. https://doi.org/10.1016/j.yrtph.2007.08.012
Laux L, Glanzmann P, Schaffner P, Spielberger CD (1981) Das State-Trait-Angstinventar (STAI). Beltz Testgesellschaft, Weinheim
Lundström JN, Frasnelli J, Larsson M, Hummel T (2005) Sex differentiated responses to intranasal trigeminal stimuli. Int J Psychophysiol 57(3):181–186. https://doi.org/10.1016/j.ijpsycho.2005.01.003
Lungu O, Potvin S, Tikàsz A, Mendrek A (2015) Sex differences in effective fronto-limbic connectivity during negative emotion processing. Psychoneuroendocrinology. 62:180–188. https://doi.org/10.1016/j.psyneuen.2015.08.012
Martinez B, Karunanayaka P, Wang J, Tobia MJ, Vasavada M, Eslinger PJ, Yang QX (2017) Different patterns of age-related central olfactory decline in men and women as quantified by olfactory fMRI. Oncotarget 8(45):79212–79222. https://doi.org/10.18632/oncotarget.16977
Monsé C, Sucker K, van Thriel C, Broding HC, Jettkant B, Berresheim H, Wiethege T, Käfferlein H, Merget R, Bünger J, Brüning T (2012) Considerations for the design and technical setup of a human whole-body exposure chamber. Inhal Toxicol 24(2):99–108. https://doi.org/10.3109/08958378.2011.640362
Monster AW, Chan HC, O’Connor D (1978) Long-term trends in human eye blink rate. Biotelem Patient Monit 5(4):206–222. https://doi.org/10.1016/0039-6257(80)90131-9
Müller JU, Bruckner T, Triebig G (2013) Exposure study to examine chemosensory effects of formaldehyde on hyposensitive and hypersensitive males. Int Arch Occup Environ Health 86(1):107–117. https://doi.org/10.1007/s00420-012-0745-9
Nakamori K, Odawara M, Nakajima T, Mizutani T, Tsubota K (1997) Blinking is controlled primarily by ocular surface conditions. Am J Ophthalmol 124(1):24–30. https://doi.org/10.1016/S0002-9394(14)71639-3
Nielsen GD, Wolkoff P (2017) Evaluation of airborne sensory irritants for setting exposure limits or guidelines: a systematic approach. Regul Toxicol Pharmacol 90:308–317. https://doi.org/10.1016/j.yrtph.2017.09.015
Nielsen GD, Wolkoff P, Alarie Y (2007) Sensory irritation: risk assessment approaches. Regul Toxicol Pharmacol 48:6–18. https://doi.org/10.1016/j.yrtph.2006.11.005
Nøjgaard JK, Christensen KB, Wolkoff P (2005) The effect on human eye blink frequency of exposure to limonene oxidation products and methacrolein. Toxicol Lett 156(2):241–251. https://doi.org/10.1016/j.toxlet.2004.11.013
Nordin S (2004) Normative data for the chemical sensitivity scale. J Environ Psychol 24(3):399–403. https://doi.org/10.1016/S0272-4944(03)00074-4
Nordin S, Millqvist E, Löwhagen O, Bende M (2003) The Chemical Sensitivity Scale: psychometric properties and comparison with the noise sensitivity scale. Journal of Environmental Psychology 23(4):357–365. https://doi.org/10.1016/S0272-4944(03)00002-1
Nordin S, Claeson A-S, Andersson M, Sommar L, Andree J, Lundqvist K (2013) Impact of health-risk perception on odor perception and cognitive performance. Chemosens Percept 6(4):190–197. https://doi.org/10.3389/fpsyg.2013.00816
Ohla K, Lundström JN (2013) Sex differences in chemosensation: sensory or emotional? Front Hum Neurosci 7:607. https://doi.org/10.3389/fnhum.2013.00607
Olofsson JK, Nordin S (2004) Gender differences in chemosensory perception and event-related potentials. Chem Senses 29(7):629–637. https://doi.org/10.1093/chemse/bjh066
Ørbæk P, Persson R, Osterberg K (2005) Impact of trait anxiety and social conformity on responses to experimental chemical challenge. Environ Toxicol Pharmacol 19(3):659–664. https://doi.org/10.1016/j.etap.2004.12.033
Pacharra M, Kleinbeck S, Schäper M, Blaszkewicz M, van Thriel C (2016a) Multidimensional assessment of self-reported chemical intolerance and its impact on chemosensory effects during ammonia exposure. Int Arch Occup Environ Health 89(6):947–959. https://doi.org/10.1007/s00420-016-1134-6
Pacharra M, Kleinbeck S, Schäper M, Juran SA, Hey K, Blaszkewicz M, Lehmann ML, Golka K, van Thriel C (2016b) Interindividual differences in chemosensory perception: toward a better understanding of perceptual ratings during chemical exposures. J Toxicol Environ Health A 79(22–23):1026–1040. https://doi.org/10.1080/15287394.2016.1219547
Pacharra M, Kleinbeck S, Schäper M, Blaszkewicz M, Golka K, van Thriel C (2017) Does seasonal allergic rhinitis increase sensitivity to ammonia exposure? Int J Hyg Environ Health 220(5):840–848. https://doi.org/10.1016/j.ijheh.2017.03.013
Petrova M, Diamond J, Schuster B, Dalton P (2008) Evaluation of trigeminal sensitivity to ammonia in asthmatics and healthy human volunteers. Inhal Toxicol 20(12):1085–1092. https://doi.org/10.1080/08958370802120396
Rethage T, Eis D, Gieler U, Nowak D, Wiesmüller GA, Lacour M, Hodapp V, Stilianakis N, Eikmann TF, Herr CE (2008) Assessment of environmental worry in health-related settings: re-evaluation and modification of an environmental worry scale. Int J Hyg Environ Health 211(1–2):105–113. https://doi.org/10.1016/j.ijheh.2007.01.030
Scheibe M, Opatz O, Hummel T (2009) Are there sex-related differences in responses to repetitive olfactory/trigeminal stimuli? Eur Arch Otorhinolaryngol 266(8):1323–1326. https://doi.org/10.1007/s00405-008-0860-0
Shusterman D, Murphy MA, Balmes J (2003) Influence of age, gender, and allergy status on nasal reactivity to inhaled chlorine. Inhal Toxicol 15(12):1179–1189. https://doi.org/10.1080/08958370390229852
Shusterman D, Tarun A, Murphy MA, Morris J (2005) Seasonal allergic rhinitic and normal subjects respond differentially to nasal provocation with acetic acid vapor. Inhal Toxicol 17(3):147–152. https://doi.org/10.1080/08958370590904508
Situ P, Simpson TL, Fonn D, Jones LW (2008) Conjunctival and corneal pneumatic sensitivity is associated with signs and symptoms of ocular dryness. Invest Ophthalmol Vis Sci 49(7):2971–2976. https://doi.org/10.1167/iovs.08-1734
Spielberger CD (1983) Manual for the State-Trait Anxiety Inventory. Consulting Psychologists Press, Palo Alto, CA
van Leeuwen JMC, Vink M, Fernández G, Hermans EJ, Joëls M, Kahn RS, Vinkers CH (2018) At-risk individuals display altered brain activity following stress. Neuropsychopharmacology 43(9):1954–1960. https://doi.org/10.1038/s41386-018-0026-8
van Thriel C, Kiesswetter E, Schäper M, Blaszkewicz M, Golka K, Seeber A (2005) An integrative approach considering acute symptoms and intensity ratings of chemosensory sensations during experimental exposures. Environ Toxicol Pharmacol 19(3):589–598. https://doi.org/10.1016/j.etap.2004.12.024
van Thriel C, Triebig G, Bolt HM (2006a) Editorial: evaluation of chemosensory effects due to occupational exposures. Int Arch Occup Environ Health 79(4):265–267. https://doi.org/10.1007/s00420-005-0058-3
van Thriel C, Schäper M, Kiesswetter E, Kleinbeck S, Juran S, Blaszkewicz M, Fricke HH, Altmann L, Berresheim H, Brüning T (2006b) From chemosensory thresholds to whole body exposures—experimental approaches evaluating chemosensory effects of chemicals. Int Arch Occup Environ Health 79(4):308–321. https://doi.org/10.1007/s00420-005-0057-4
van Thriel C, Kleinbeck S, Schaeper M, Blaszkewicz M, Golka K, Lehmann M, Brüning T (2012) Health effects of irritants—which role does age play? (Gesundheitliche Effekte durch Reizstoffe—welche Rolle spielt das Lebensalter?) Arbeitsmed. Sozialmed Umweltmed 47(3):126
Wålinder R, Ernstgård L, Norbäck D, Wieslander G, Johanson G (2008) Acute effects of 1-octen-3-ol, a microbial volatile organic compound (MVOC)—an experimental study. Toxicol Lett 181(3):141–147. https://doi.org/10.1016/j.toxlet.2008.07.013
Wintermann GB, Donix M, Joraschky P, Gerber J, Petrowski K (2013) Altered olfactory processing of stress-related body odors and artificial odors in patients with panic disorder. PLoS One 8(9):e74655. https://doi.org/10.1371/journal.pone.0074655
Yolton DP, Yolton RL, López R, Bogner B, Stevens R, Rao D (1994) The effects of gender and birth control pill use on spontaneous blink rates. J Am Optom Assoc 65(11):763–770
Acknowledgements
The authors would like to thank all participants as well as the staff of the working group for conduction the experiment and the extensive chemical and physiological analyses.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Sucker, K., Hoffmeyer, F., Monsé, C. et al. Ethyl acrylate: influence of sex or atopy on perceptual ratings and eye blink frequency. Arch Toxicol 93, 2913–2926 (2019). https://doi.org/10.1007/s00204-019-02568-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-019-02568-6