Advertisement

Archives of Toxicology

, Volume 88, Issue 5, pp 1127–1140 | Cite as

Neurobehavioral performance in volunteers after inhalation of white spirits with high and low aromatic content

  • S. A. Juran
  • G. Johanson
  • L. Ernstgård
  • A. Iregren
  • C. van Thriel
Organ Toxicity and Mechanisms

Abstract

The content of aromatic hydrocarbons in solvent mixtures, such as white spirits (WS), has been assumed a major contributor to the neurotoxic effects of these compounds. Hence, dearomatized WS have been introduced to the market rapidly in the last decade. Studies investigating other aromatic hydrocarbons (toluene) and animal models have supported the aforementioned assumption, but the current study is the first one to compare acute neurobehavioral effects of exposure to aromatic and dearomatized WS (aWS, daWS) content in human volunteers at current occupational exposure limit values. In a pseudo-randomized crossover design, six female and six male healthy volunteers were exposed to aWS and daWS at two concentrations (100 and 300 mg/m3) and to clean air for 4 h at rest. During each of the five exposure conditions, volunteers performed five neurobehavioral tasks that were selected following a multidisciplinary approach that accounted for findings from the cognitive neurosciences and mechanisms of solvent toxicity. Two of the tasks indicated performance changes during aromatic WS exposure, the working memory (WM) and the response shifting task, but both effects are difficult to interpret due to low mean accuracy in the WM task and due to a lack of dose–response relationship in the response shifting task. Healthy human volunteers showed weak and inconsistent neurobehavioral impairment after 4-h exposures to 100 and 300 mg/m3 aromatic or dearomatized WS. Our multidisciplinary approach of selecting neurobehavioral test methods may guide the test selection strategies in future studies.

Keywords

Dose-response relationship Solvent neurotoxicity Acute inhalation exposure Occupational exposure limit Mineral spirits Stoddard solvent 

Notes

Acknowledgments

We are grateful to Mr Birger Lind for skillful technical assistance and to Dr. Bengt Sjögren for medical support during the study. The study was performed at the Unit of Work Environment Toxicology (Karolinska Institutet, Stockholm, Sweden) in collaboration with the Unit for Neurotoxicology and Chemosensation (Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany).

References

  1. Aalto S, Bruck A, Laine M, Nagren K, Rinne JO (2005) Frontal and temporal dopamine release during working memory and attention tasks in healthy humans: a positron emission tomography study using the high-affinity dopamine D2 receptor ligand [11C]FLB 457. J Neurosci 25(10):2471–2477PubMedCrossRefGoogle Scholar
  2. Arnsten AF, Li BM (2005) Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry 57(11):1377–1384PubMedCrossRefGoogle Scholar
  3. Aron AR, Robbins TW, Poldrack RA (2004) Inhibition and the right inferior frontal cortex. Trends Cogn Sci 8(4):170–177PubMedCrossRefGoogle Scholar
  4. Baelum J, Andersen IB, Lundqvist GR, Mølhave L, Pedersen OF, Vaeth M, Wyon DP (1985) Response of solvent-exposed printers and unexposed controls to six-hour toluene exposure. Scand J Work Environ Health 11(4):271–280PubMedCrossRefGoogle Scholar
  5. Bale AS, Smothers CT, Woodward JJ (2002) Inhibition of neuronal nicotinic acetylcholine receptors by the abused solvent, toluene. Br J Pharmacol 137:375–383PubMedCentralPubMedCrossRefGoogle Scholar
  6. Bale AS, Meacham CA, Benignus VA, Bushnell PJ, Shafer TJ (2005a) Volatile organic compounds inhibit human and rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. Toxicol Appl Pharmacol 205:77–88PubMedCrossRefGoogle Scholar
  7. Bale AS, Tu Y, Carpenter-Hyland EP, Chandler LJ, Woodward JJ (2005b) Alterations in glutamatergic and gabaergic ion channel activity in hippocampal neurons following exposure to the abused inhalant toluene. Neuroscience 130:197–206PubMedCrossRefGoogle Scholar
  8. Balster RL (1998) Neural basis of inhalant abuse. Drug Alcohol Depend 51(1–2):207–214PubMedCrossRefGoogle Scholar
  9. Benignus VA, Boyes WK, Bushnell PJ (1998) A dosimetric analysis of behavioral effects of acute toluene exposure in rats and humans. Toxicol Sci 43(2):186–195. doi: 10.1006/toxs.1998.2458 PubMedGoogle Scholar
  10. Benignus VA, Geller AM, Boyes WK, Bushnell PJ (2005) Human neurobehavioral effects of long-term exposure to styrene: a meta-analysis. Environ Health Perspect 113(5):532–538. doi: 10.1289/ehp.7518 PubMedCentralPubMedCrossRefGoogle Scholar
  11. Bertolino A, Taurisano P, Pisciotta NM, Blasi G, Fazio L, Romano R, Gelao B, Lo Bianco L, Lozupone M, Di Giorgio A, Caforio G, Sambataro F, Niccoli-Asabella A, Papp A, Ursini G, Sinibaldi L, Popolizio T, Sadee W, Rubini G (2010) Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance. PLoS ONE 5(2):e9348. doi: 10.1371/journal.pone.0009348 PubMedCentralPubMedCrossRefGoogle Scholar
  12. Beste C, Baune BT, Domschke K, Falkenstein M, Konrad C (2010) Dissociable influences of NR2B-receptor related neural transmission on functions of distinct associative basal ganglia circuits. Neuroimage 52(1):309–315. doi: 10.1016/j.neuroimage.2010.04.022 PubMedCrossRefGoogle Scholar
  13. Bowen SE, Batis JC, Paez-Martinez N, Cruz SL (2006) The last decade of solvent research in animal models of abuse: mechanistic and behavioral studies. Neurotoxicol Teratol 28(6):636–647. doi: 10.1016/j.ntt.2006.09.005 PubMedCrossRefGoogle Scholar
  14. Brouwer B, Culham EG, Liston RA, Grant T (1998) Normal variability of postural measures: implications for the reliability of relative balance performance outcomes. Scand J Rehabil Med 30(3):131–137PubMedCrossRefGoogle Scholar
  15. Buckert M, Kudielka BM, Reuter M, Fiebach CJ (2012) The COMT Val158Met polymorphism modulates working memory performance under acute stress. Psychoneuroendocrinology 37(11):1810–1821. doi: 10.1016/j.psyneuen.2012.03.014 PubMedCrossRefGoogle Scholar
  16. Bushnell PJ, Kavlock RJ, Crofton KM, Weiss B, Rice DC (2010) Behavioral toxicology in the 21st century: challenges and opportunities for behavioral scientists. Summary of a symposium presented at the annual meeting of the neurobehavioral teratology society, June, 2009. Neurotoxicol Teratol 32(3):313–328. doi: 10.1016/j.ntt.2010.02.002 PubMedCrossRefGoogle Scholar
  17. Carbonnell L, Falkenstein M (2006) Does the error negativity reflect the degree of response conflict? Brain Res 1095(1):124–130PubMedCrossRefGoogle Scholar
  18. Chudasama Y, Robbins TW (2006) Functions of frontostriatal systems in cognition: comparative neuropsychopharmacological studies in rats, monkeys and humans. Biol Psychol 73(1):19–38. doi: 10.1016/j.biopsycho.2006.01.005 PubMedCrossRefGoogle Scholar
  19. Cintra A, Andbjer B, Finnman UB, Hagman M, Agnati LF, Höglund G, Fuxe K (1996) Subacute toluene exposure increases DA dysfunction in the 6-OH dopamine lesioned nigrostriatal dopaminergic system of the rat. Neurosci Lett 217(1):61–65. doi: 10.1016/0304-3940(96)13049-4 PubMedCrossRefGoogle Scholar
  20. Cintra A, Aguirre JA, Andbjer B, Finnman UB, Hagman M, Agnati LF, Fuxe K (1999) Subchronic toluene exposure in low concentrations produces signs of reduced dysfunction in the 6-hydroxydopamine lesioned nigrostriatal dopaminergic system of the rat. Neurosci Lett 274(1):5–8PubMedCrossRefGoogle Scholar
  21. Cohr KH, Stokholm J, Bruhn P (1980) Neurologic response to white spirit exposure. Dev Toxicol Environ Sci 8:95–102PubMedGoogle Scholar
  22. Cruz SL, Mirshahi T, Thomas B, Balster RL, Woodward JJ (1998) Effects of the abused solvent toluene on recombinant N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors expressed in Xenopus oocytes. J Pharmacol Exp Ther 286(1):334–340PubMedGoogle Scholar
  23. Dick FD (2006) Solvent neurotoxicity. Occup Environ Med 63(3):221–226. doi: 10.1136/oem.2005.022400 PubMedCentralPubMedCrossRefGoogle Scholar
  24. Echeverria D, Fine L, Langolf G, Schork A, Sampaio C (1989) Acute neurobehavioural effects of toluene. Br J Ind Med 46(7):483–495PubMedCentralPubMedGoogle Scholar
  25. Ernstgard L, Iregren A, Juran S, Sjogren B, van Thriel C, Johanson G (2009a) Acute effects of exposure to vapours of standard and dearomatized white spirits in humans. 2. Irritation and inflammation. J Appl Toxicol 29(3):263–274. doi: 10.1002/jat.1407 PubMedCrossRefGoogle Scholar
  26. Ernstgard L, Lind B, Johanson G (2009b) Acute effects of exposure to vapours of standard and dearomatized white spirits in humans. 1. Dose-finding study. J Appl Toxicol 29(3):255–262. doi: 10.1002/jat.1408 PubMedCrossRefGoogle Scholar
  27. Gamberale F, Annwall G, Hultengren M (1975) Exposure to white spirit. II. Psychological functions. Scand J Work Environ Health 1(1):31–39PubMedCrossRefGoogle Scholar
  28. Gobba F, Cavalleri A (2003) Color vision impairment in workers exposed to neurotoxic chemicals. Neurotoxicology 24(4–5):693–702PubMedCrossRefGoogle Scholar
  29. Gulick D, Gould TJ (2007) Acute ethanol has biphasic effects on short- and long-term memory in both foreground and background contextual fear conditioning in C57BL/6 mice. Alcohol Clin Exp Res 31(9):1528–1537PubMedCentralPubMedCrossRefGoogle Scholar
  30. Herpin G, Gauchard GC, Vouriot A, Hannhart B, Barot A, Mur JM, Zmirou-Navier D, Perrin PP (2008) Impaired neuromotor functions in hospital laboratory workers exposed to low levels of organic solvents. Neurotox Res 13(3–4):185–196PubMedCrossRefGoogle Scholar
  31. Herpin G, Gargouri I, Gauchard GC, Nisse C, Khadhraoui M, Elleuch B, Zmirou-Navier D, Perrin PP (2009) Effect of chronic and subchronic organic solvents exposure on balance control of workers in plant manufacturing adhesive materials. Neurotox Res 15(2):179–186. doi: 10.1007/s12640-009-9018-0 PubMedCrossRefGoogle Scholar
  32. Hodgkinson L, Prasher D (2006) Effects of industrial solvents on hearing and balance: a review. Noise Health 8(32):114–133PubMedCrossRefGoogle Scholar
  33. IPCS (1996) White spirit (Stoddard solvent). International programme on chemical safety. World Health Organization, GenevaGoogle Scholar
  34. Iregren A, Andersson M, Nylen P (2002) Color vision and occupational chemical exposures: I. An overview of tests and effects. Neurotoxicology 23(6):719–733PubMedCrossRefGoogle Scholar
  35. Juran SA, van Thriel C, Kleinbeck S, Schaper M, Falkenstein M, Iregren A, Johanson G (2012) Neurobehavioral performance in human volunteers during inhalation exposure to the unpleasant local irritant cyclohexylamine. Neurotoxicology 33(5):1180–1187. doi: 10.1016/j.neuro.2012.06.014 PubMedCrossRefGoogle Scholar
  36. Kleinsorge T (2004) Hierarchical switching with two types of judgment and two stimulus dimensions. Exp Psychol 51(2):145–149PubMedCrossRefGoogle Scholar
  37. Lammers JH, Emmen HH, Muijser H, Hoogendijk EM, McKee RH, Owen DE, Kulig BM (2007) Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents II. Neurobehavioral effects of white spirit in rat and human. Neurotoxicology 28(4):736–750. doi: 10.1016/j.neuro.2007.03.003 PubMedCrossRefGoogle Scholar
  38. Lanthony P (1978) The desaturated panel D-15. Documenta Ophthalmol 46(1):185–189Google Scholar
  39. Lim J, Ebstein R, Tse CY, Monakhov M, Lai PS, Dinges DF, Kwok K (2012) Dopaminergic polymorphisms associated with time-on-task declines and fatigue in the Psychomotor Vigilance Test. PLoS ONE 7(3):e33767. doi: 10.1371/journal.pone.0033767 PubMedCentralPubMedCrossRefGoogle Scholar
  40. Lo PS, Wu CY, Sue HZ, Chen HH (2009) Acute neurobehavioral effects of toluene: involvement of dopamine and NMDA receptors. Toxicology 265(1–2):34–40. doi: 10.1016/j.tox.2009.09.005 PubMedCrossRefGoogle Scholar
  41. Lomax RB, Ridgway P, Meldrum M (2004) Does occupational exposure to organic solvents affect colour discrimination? Toxicol Rev 23(2):91–121PubMedCrossRefGoogle Scholar
  42. Mergler D, Blain L, Lagacé JP (1987) Solvent related colour vision loss: an indicator of neural damage? Int Arch Occup Environ Health 59(4):313–321PubMedCrossRefGoogle Scholar
  43. Meyer-Baron M, Blaszkewicz M, Henke H, Knapp G, Muttray A, Schaper M, van Thriel C (2008) The impact of solvent mixtures on neurobehavioral performance: conclusions from epidemiological data. Neurotoxicology 29(3):349–360. doi: 10.1016/j.neuro.2008.02.005 PubMedCrossRefGoogle Scholar
  44. Moykkynen T, Korpi ER (2012) Acute effects of ethanol on glutamate receptors. Basic Clin Pharmacol Toxicol 111(1):4–13. doi: 10.1111/j.1742-7843.2012.00879.x PubMedGoogle Scholar
  45. Mutti A, Falzoi M, Romanelli A, Bocchi MC, Ferroni C, Franchini I (1988) Brain dopamine as a target for solvent toxicity: effects of some monocyclic aromatic hydrocarbons. Toxicology 49(1):77–82PubMedCrossRefGoogle Scholar
  46. Nielsen GD, Lund SP, Ladefoged O (2006) Neurological effects of white spirit: contribution of animal studies during a 30-year period*. Basic Clin Pharmacol Toxicol 98(2):115–123PubMedCrossRefGoogle Scholar
  47. Nordin SBA, Lidén E, Bende M (1998) The Scandinavian Odor-Identification Test: development, reliability, validity and normative data. Acta Otolaryngol 118(2):226–234. doi: 10.1080/00016489850154946 PubMedCrossRefGoogle Scholar
  48. Paramei GV, Meyer-Baron M, Seeber A (2004) Impairments of colour vision induced by organic solvents: a meta-analysis study. Neurotoxicology 25(5):803–816PubMedCrossRefGoogle Scholar
  49. Parasuraman R, Warm J, See J (2000) Brain systems of vigilance. In: Parasuraman R (ed) The attentive brain. MIT Press, Cambridge, pp 221–256Google Scholar
  50. Rahill AA, Weiss B, Morrow PE, Frampton MW, Cox C, Gibb R, Gelein R, Speers D, Utell MJ (1996) Human performance during exposure to toluene. Aviat Space Environ Med 67(7):640–647PubMedGoogle Scholar
  51. Riegel AC, French ED (1999) Acute toluene induces biphasic changes in rat spontaneous locomotor activity which are blocked by remoxipride. Pharmacol Biochem Behav 62(3):399–402PubMedCrossRefGoogle Scholar
  52. Røgind H, Lykkegaard JJ, Bliddal H, Danneskiold-Samsøe B (2003) Postural sway in normal subjects aged 20–70 years. Clin Physiol Funct Imaging 23(3):171–176PubMedCrossRefGoogle Scholar
  53. Romanelli A, Falzoi M, Mutti A, Bergamaschi E, Franchini I (1986) Effects of some monocyclic aromatic solvents and their metabolites on brain dopamine in rabbits. J Appl Toxicol 6(6):431–436PubMedCrossRefGoogle Scholar
  54. Savolainen K, Linnavuo M (1979) Effects of m-xylene on human equilibrium measured with a quantitative method. Acta Pharmacol Toxicol (Copenh) 44(4):315–318CrossRefGoogle Scholar
  55. Schaper M, Demes P, Kiesswetter E, Zupanic M, Seeber A (2004) Colour vision and occupational toluene exposure: results of repeated examinations. Toxicol Lett 151(1):193–202PubMedCrossRefGoogle Scholar
  56. SCOEL (2007) Recommendation of the Scientific Committee on Occupational Exposure Limits for “White Spirit”. http://ec.europa.eu/social/BlobServlet?docId=3859&langId=en
  57. Sethre T, Laubli T, Berode M, Krueger H (2000) Neurobehavioural effects of experimental isopropanol exposure. Int Arch Occup Environ Health 73(2):105–112PubMedCrossRefGoogle Scholar
  58. Smargiassi A, Mutti A, Bergamaschi E, Belanger S, Truchon G, Mergler D (1996) Pilot study of peripheral markers of catecholaminergic systems among workers occupationally exposed to toluene. Neurotoxicology 17(3–4):769–775PubMedGoogle Scholar
  59. SPIN (2007). Substances in Preparations in Nordic Countries. http://www.spin2000.net. Substances in preparations in Nordic Countries (2007)
  60. van Valen E, van Thriel C, Akila R, Nilson LN, Bast-Pettersen R, Sainio M, van Dijk F, van der Laan G, Verberk M, Wekking E (2012) Chronic solvent-induced encephalopathy: European consensus of neuropsychological characteristics, assessment, and guidelines for diagnostics. Neurotoxicology 33(4):710–726. doi: 10.1016/j.neuro.2012.03.010 PubMedCrossRefGoogle Scholar
  61. Vingrys AJ, King-Smith PE (1988) A quantitative scoring technique for panel tests of color vision. Invest Ophthalmol Vis Sci 29(1):50–63PubMedGoogle Scholar
  62. Visser I, Lavini C, Booij J, Reneman L, Majoie C, de Boer AG, Wekking EM, de Joode EA, van der Laan G, van Dijk FJ, Schene AH, Den Heeten GJ (2008) Cerebral impairment in chronic solvent-induced encephalopathy. Ann Neurol 63(5):572–580PubMedCrossRefGoogle Scholar
  63. von Euler G, Ögren SO, Bondy SC, McKee M, Warner M, Gustafsson JÅ, Fuxe K (1991) Subacute exposure to low concentrations of toluene affects dopamine-mediated locomotor activity in the rat. Toxicology 67(3):333–349. doi: 10.1016/0300-483X(91)90032-V CrossRefGoogle Scholar
  64. von Euler G, Ogren SO, Li XM, Fuxe K, Gustafsson JA (1993) Persistent effects of subchronic toluene exposure on spatial learning and memory, dopamine-mediated locomotor activity and dopamine D2 agonist binding in the rat. Toxicology 77(3):223–232CrossRefGoogle Scholar
  65. von Euler G, Ogren SO, Eneroth P, Fuxe K, Gustafsson JA (1994) Persistent effects of 80 ppm toluene on dopamine-regulated locomotor activity and prolactin secretion in the male rat. Neurotoxicology 15(3):621–624Google Scholar
  66. White RF, Proctor SP (1997) Solvents and neurotoxicity. Lancet 349(9060):1239–1243PubMedCrossRefGoogle Scholar
  67. Yamawaki S, Sarai K (1982) Effects of toluene inhalation on locomotor activity and brain catecholamine levels in rats. Yakubutsu Seishin Kodo 2(1):57–59PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • S. A. Juran
    • 1
    • 2
  • G. Johanson
    • 1
  • L. Ernstgård
    • 1
  • A. Iregren
    • 3
  • C. van Thriel
    • 2
  1. 1.Institute of Environmental Medicine, Work Environment ToxicologyKarolinska InstitutetStockholmSweden
  2. 2.Leibniz Research Centre for Working Environment and Human Factors, Neurotoxicology and ChemosensationDortmundGermany
  3. 3.Swedish Work Environment AuthorityToxicological Risk AssessmentStockholmSweden

Personalised recommendations