Research Article| Volume 121, P60-67, June 2017

Levels of oxylipins, endocannabinoids and related lipids in plasma before and after low-level exposure to acrolein in healthy individuals and individuals with chemical intolerance


      • Effects of exposure to acrolein upon plasma oxylipin, endocannabinoid and related lipid levels were investigated.
      • Individuals with chemical intolerance (CI) an affliction with a suggested inflammatory origin and controls, were included.
      • Low-level exposure to acrolein did not affect levels of oxylipins, endocannbinoids or related lipids in plasma.
      • The difference in sensory perception in CI compared to controls could not be associated with levels of lipid mediators.


      Oxylipins and endocannabinoids play important biological roles, including effects upon inflammation. It is not known whether the circulating levels of these lipids are affected by inhalation of the environmental pollutant acrolein. In the present study, we have investigated the consequences of low-level exposure to acrolein on oxylipin, endocannabinoid and related lipid levels in the plasma of healthy individuals and individuals with chemical intolerance (CI), an affliction with a suggested inflammatory origin. Participants were exposed twice (60 min) to heptane and a mixture of heptane and acrolein. Blood samples were collected before exposure, after and 24 h post-exposure. There were no overt effects of acrolein exposure on the oxylipin lipidome or endocannibinoids detectable in the bloodstream at the time points investigated. No relationship between basal levels or levels after exposure to acrolein and CI could be identified. This implicates a minor role of inflammatory mediators on the systemic level in CI.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Prostaglandins, Leukotrienes and Essential Fatty Acids
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Beauchamp R.O.
        • Andjelkovich D.A.
        • Kligerman A.D.
        • Morgan K.T.
        • Heck H.D.
        A critical review of the literature on acrolein toxicity.
        Crit. Rev. Toxicol. 1985; 14: 309-380
        • Bein K.
        • Leikauf G.D.
        Acrolein - a pulmonary hazard.
        Mol. Nutr. Food Res. 2011; 55: 1342-1360
        • Faroon O.
        • Roney N.
        • Taylor J.
        • Ashizawa A.
        • Lumpkin M.H.
        • Plewak D.J.
        Acrolein environmental levels and potential for human exposure.
        Toxicol. Ind. Health. 2008; 24: 543-564
      1. Arbetsmiljöverket, Hygieniska gränsvärden, Arbetsmiljöverkets Föreskrifter Och Allmänna Råd Om Hyg. Gränsvärden (in Swedish). AFS 2011:1 (2011).

        • Weber-Tschopp A.
        • Fischer T.
        • Gierer R.
        • Grandjean E.
        Experimentally induced irritating effects of acrolein on men (author's transl).
        Int. Arch. Occup. Environ. Health. 1977; 40: 117-130
        • Claeson A.-S.
        • Lind N.
        Human exposure to acrolein: time-dependence and individual variation in eye irritation.
        Environ. Toxicol. Pharmacol. 2016; 45: 20-27
        • Dwivedi A.M.
        • Johanson G.
        • Lorentzen J.C.
        • Palmberg L.
        • Sjögren B.
        • Ernstgård L.
        Acute effects of acrolein in human volunteers during controlled exposure.
        Inhal. Toxicol. 2015; 8378: 1-12
        • Macpherson L.J.
        • Dubin A.E.
        • Evans M.J.
        • Marr F.
        • Schultz P.G.
        • Cravatt B.F.
        • Patapoutian A.
        Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines.
        Nature. 2007; 445: 541-545
        • Bessac B.F.
        • Jordt S.-E.
        • Brethtaking
        TRP channels: TRPA1 and TRPV1 in airway chemosensation and rexlex control.
        Physiology. 2008; : 360-370
        • Andrè E.
        • Campi B.
        • Materazzi S.
        • Trevisani M.
        • Amadesi S.
        • Massi D.
        • Creminon C.
        • Vaksman N.
        • Nassini R.
        • Civelli M.
        • Baraldi P.G.
        • Poole D.P.
        • Bunnett N.W.
        • Geppetti P.
        • Patacchini R.
        Cigarette smoke–induced neurogenic inflammation is mediated by α,β-unsaturated aldehydes and the TRPA1 receptor in rodents.
        J. Clin. Invest. 2008; 118
        • Bautista D.M.
        • Pellegrino M.
        • Tsunozaki M.
        TRPA1: a gatekeeper for inflammation.
        Annu. Rev. Physiol. 2013; 75: 181-200
        • Wang S.
        • Dai Y.
        • Fukuoka T.
        • Yamanaka H.
        • Kobayashi K.
        • Obata K.
        • Cui X.
        • Tominaga M.
        • Noguchi K.
        • Phospholipase
        C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain.
        Brain. 2008; 131: 1241-1251
        • Sisignano M.
        • Bennett D.L.H.
        • Geisslinger G.
        • Scholich K.
        TRP-channels as key integrators of lipid pathways in nociceptive neurons.
        Prog. Lipid Res. 2013; 53: 93-107
        • Johansson A.
        • Brämerson A.
        • Millqvist E.
        • Nordin S.
        • Bende M.
        Prevalence and risk factors for self-reported odour intolerance: the Skövde population-based study.
        Int. Arch. Occup. Environ. Health. 2005; 78: 559-564
        • Berg N.D.
        • Linneberg A.
        • Dirksen A.
        • Elberling J.
        Prevalence of self-reported symptoms and consequences related to inhalation of airborne chemicals in a Danish general population.
        Int. Arch. Occup. Environ. Health. 2008; 81: 881-887
        • Caress S.M.
        • Steinemann A.C.
        Prevalence of multiple chemical sensitivities: a population-based study in the southeastern United States.
        Am. J. Public Health. 2004; 94: 746-747
        • Kreutzer R.
        • Neutra R.
        • Lashuay N.
        Prevalence of people reporting sensitivities to chemicals in a population-based survey.
        Am. J. Epidemiol. 1999; 150: 1-12
        • Söderholm A.
        • Söderberg A.
        • Nordin S.
        The experience of living with sensory hyperreactivity-accessibility, financial security, and social relationships.
        Health Care Women Int. 2011; 32: 686-707
        • Bascom R.
        • Meggs W.J.
        • Frampton M.
        • Hudnell K.
        • Killburn K.
        • Kobal G.
        • Medinsky M.
        • Rea W.
        Neurogenic inflammation: with additional discussion of central and perceptual integration of nonneurogenic inflammation.
        Environ. Health Perspect. 1997; 105: 531-537
        • De Luca C.
        • Scordo M.G.
        • Cesareo E.
        • Pastore S.
        • Mariani S.
        • Maiani G.
        • Stancato A.
        • Loreti B.
        • Valacchi G.
        • Lubrano C.
        • Raskovic D.
        • De Padova L.
        • Genovesi G.
        • Korkina L.G.
        Biological definition of multiple chemical sensitivity from redox state and cytokine profiling and not from polymorphisms of xenobiotic-metabolizing enzymes.
        Toxicol. Appl. Pharmacol. 2010; 248: 285-292
        • Dantoft T.M.
        • Elberling J.
        • Brix S.
        • Szecsi P.B.
        • Vesterhauge S.
        • Skovbjerg S.
        An elevated pro-inflammatory cytokine profile in multiple chemical sensitivity.
        Psychoneuroendocrinology. 2013;
        • Meggs W.J.
        • Cleveland C.H.
        Rhinolaryngoscopic examination of patients with the multiple chemical sensitivity syndrome.
        Arch. Environ. Health. 1993; 48: 14-18
        • Kimata H.
        Effect of exposure to volatile organic compounds on plasma levels of neuropeptides, nerve growth factor and histamine in patients with self-reported multiple chemical sensitivity.
        Int. J. Hyg. Environ. Health. 2004; 207: 159-163
        • Dantoft T.M.
        • Skovbjerg S.
        • Andersson L.
        • Claeson A.-S.
        • Lind N.
        • Nordin S.
        • Brix S.
        Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity.
        PLoS One. 2015; 10: e0143534
        • Nordin S.
        The Chemical Sensitivity Scale: psychometric properties and comparison with the noise sensitivity scale.
        J. Environ. Psychol. 2003; 23: 359-367
        • Levenstein S.
        • Prantera C.
        • Varvo V.
        • Scribano M.L.
        • Berto E.
        Development of the perceived stress questionnaire: a new tool for psychosomatic research.
        J. Psychosom. Res. 1993; 37: 19-32
        • Cain W.S.
        Testing olfaction in a clinical setting.
        Ear, Nose Throat J. 1989; 68: 316-328
        • Devlin R.B.
        • McDonnell W.F.
        • Becker S.
        • Madden M.C.
        • McGee M.P.
        • Perez R.
        • Hatch G.
        • House D.E.
        • Koren H.S.
        Time-dependent changes of inflammatory mediators in the lungs of humans exposed to 0.4ppm ozone for 2hr: a comparison of mediators found in broncoalveolar lavage fluid 1 and 18h after exposure.
        Toxicol. Appl. Pharmacol. 1996; 138: 176-185
        • Vaart H. Van Der
        • Postma D.S.
        • Timens W.
        • ten Hacken N.H.
        Acute effects of cigarette smoke on inflammation and oxidative stress: a review.
        Thorax. 2004; 59: 713-721
        • Claeson A.-S.
        • Andersson L.
        Symptoms from masked acrolein exposure suggest altered trigeminal reactivity in chemical intolerance.
        Neurotoxicology. 2017; 60: 92-98
        • Gouveia-Figueira S.
        • Späth J.
        • Zivkovic A.M.
        • Nording M.L.
        Profiling the oxylipin and endocannabinoid metabolome by UPLC-ESI-MS/MS in human plasma to monitor postprandial inflammation.
        PLoS One. 2015; 10: 1-29
        • Gouveia-Figueira S.
        • Nording M.L.
        Development and validation of a sensitive UPLC-ESI-MS/MS method for the simultaneous quantification of 15 endocannabinoids and related compounds in milk and other biofluids.
        Anal. Chem. 2014; 86: 1186-1195
        • Little R.
        A test of missing completely at random for multivariate data with missing values.
        J. Am. Stat. Assoc. 1988; 83: 1198-1202
        • Box G.
        • An C.D.R.
        analysis of transformations.
        J. R. Stat. Soc. Ser. B. 1964; 26: 211-252
        • Team R.D.C.
        R: A Language and Environment for Statistical Computing.
        the R Foundation for Statistical Computing, Vienna, Austria2011
        • Venables W.N.
        • Ripley B.D.
        Modern Applied Statistics with S. 4th ed. Springer, New York2002
        • Benjamini Y.
        • Hochberg Y.
        Controlling the false discovery rate: a practical and powerful approach to multiple testing.
        J. R. Stat. Soc. Ser. B. 1995; 57: 289-300
        • D B.
        • M M.
        • B B.
        • S W.
        Fitting linear mixed-effects models using lme4.
        J. Stat. Softw. 2015; 67: 1-48
      2. K. A, B. PB, Bojesen Christensen RH, lmerTest: Tests in Linear Mixed Effects Models. R package, (2015).

        • Wilcox R.
        How many discoveries have been lost by ignoring modern statistical methods?.
        Am. Psychol. 1998; 53: 300-303
        • Wilcox R.
        Modern statistics for the social and behavioral sciences. A practical introduction.
        CRC Press, Boca Raton2012
        • LI-K L.
        A concordance correlation coefficient to evaluate reproducibility.
        Biometrics. 1989; 45: 255-268
        • PE S.
        • JL F.
        Intraclass correlations: uses in assessing rater reliability.
        Psychol. Bull. 1979; 420: 420-428
        • Willenberg I.
        • Ostermann A.I.
        • Schebb N.H.
        Targeted metabolomics of the arachidonic acid cascade: current state and challenges of LC-MS analysis of oxylipins.
        Anal. Bioanal. Chem. 2015; 407: 2675-2683
        • Nording M.L.
        • Yang J.
        • Georgi K.
        • Hegedus Karbowski C.
        • German J.B.
        • Weiss R.H.
        • Hogg R.J.
        • Trygg J.
        • Hammock B.D.
        • Zivkovic A.M.
        Individual variation in lipidomic profiles of healthy subjects in response to omega-3 fatty acids.
        PLoS One. 2013; 8: 1-15
        • Gouveia-Figueira S.
        • Bosson J.A.
        • Unosson J.
        • Behndig A.F.
        • Nording M.L.
        • Fowler C.J.
        Relative and absolute reliability of measures of linoleic acid-derived oxylipins in human plasma.
        Prostaglandins Other Lipid Mediat. 2015; 121: 227-233
      3. J. Fleiss, Reliability of measurement, in: N.Y.J.W.& Sons (Ed.), Des. Anal. Clin. Exp., 1986: pp. 1–32.

        • De Luca C.
        • Scordo G.
        • Cesareo E.
        • Raskovic D.
        • Genovesi G.
        • Korkina L.
        Idiopathic environmental intolerances (IEI): from molecular epidemiology to molecular medicine.
        Indian J. Exp. Biol. 2010; 48: 625-635
        • Berg N.D.
        • Linneberg A.
        • Dirksen A.
        • Elberling J.
        Prevalence of self-reported symptoms and consequences related to inhalation of airborne chemicals in a Danish general population.
        Int. Arch. Occup. Environ. Health. 2008; 81: 881-887