Toxicological Effects of Simultaneous Exposure to Toluene and Noise on some Sexual and Stress Parameters in New Zealand White Rabbits

Document Type : Original Research Paper


1 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Occupational Health Engineering, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran

5 Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran



Noise and toluene are among the numerous physical and chemical pollutants that can induce adverse effects on different body tissues and systems; nevertheless, most studies have only experimented the auditory changes induced by co-exposure to them. The present in-vivo study aimed to examine the endocrine effects of co-exposure to toluene and noise on the testes and adrenal glands. In this experimental study, 24 healthy male New Zealand White rabbits were used. The noise intensity was 100 dB (white noise) and the toluene concentration was 1000 ppm for two consecutive weeks. The luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, cortisol and adrenocorticotropic hormone (ACTH) were measured using the enzyme-linked immunosorbent assay (ELISA) method. The hematoxylin and eosin stain method (H&E) was performed for the histopathological analysis. Comparing different parameters in different groups on post-exposure days was carried out using GEE (generalized estimating equations) method. The results indicated that noise and toluene increased cortisol, LH and FSH levels during different days after the exposure. Exposure to toluene and noise made vacuolization and reduction of primary spermatogonial cells in the testes. Moreover, lymphocyte infiltration, congestion, swelling and vacuolization were detected in adrenal glands through exposure to toluene and noise. Toluene and noise induced different destructive effects on the endocrine system. More studies are required to elucidate other endocrine changes induced by exposure to toluene and noise.


Abouee-Mehrizi, A., Rasoulzadeh, Y., Kazemi, T. and Mesgari-Abbasi, M. (2020a) Inflammatory and immunological changes caused by noise exposure: A systematic review. Journal of Environmental Science and Health, Part C, 38; 61-90. 
Abouee-Mehrizi, A., Rasoulzadeh, Y., Mesgari-Abbasi, M., Mehdipour, A. and Ebrahimi-Kalan, A. (2020b). Nephrotoxic effects caused by co-exposure to noise and toluene in New Zealand white rabbits: A biochemical and histopathological study. Life sciences, 259; 118254.
Abouee-Mehrizi, A., Rasoulzadeh, Y., Mehdipour, A., Alihemmati, A. and  Rahimi, E. (2021). Hepatotoxic effects caused by simultaneous exposure to noise and toluene in New Zealand white rabbits: a biochemical and histopathological study. Ecotoxicology, 30(1); 154-163. 
Abouee-Mehrizi, A., Rasoulzadeh, Y., Kazemi, T., Mehdipour, A. andMesgari-Abbasi, M. (2022). Toxicopathological changes induced by combined exposure to noise and toluene in New Zealand White rabbits. Archives of Industrial Hygiene and Toxicology, 73(1); 31-42.
Atlanta, Georgia, USA. Wang, L.K., Pereira, N.C., Hung, Y.T. (2010). Advanced Air and Noise Pollution Control (pp. 441-452) New Jersey: Humana Press
Amsterdam, J.D., Maislin, G., Gold, P. and Winokur, A. (1989). The assessment of abnormalities in hormonal responsiveness at multiple levels of the hypothalamic-pituitary-adrenocortical axis in depressive illness. Psychoneuroendocrinology, 14; 43-62. 
Bluhm, G.L., Berglind, N., Nordling, E. and Rosenlund, M. (2007). Road traffic noise and hypertension, Occup. Environ. Med, 64; 122-126.
Board, O.S. (2017). Approaches to Understanding the Cumulative Effects of Stressors on Marine Mammals. National Academies Press, Washington, USA. 
Breen, K.M. and Mellon, P.L. (2014). Influence of stress-induced intermediates on gonadotropin gene expression in gonadotrope cells. Mol Cell Endocrinol, 385; 71-77.
Brown, J.S. (2008). Environmental and Chemical Toxins and Psychiatric Illness. American Psychiatric Publishing, Washington, USA.
Cobo, P., Murillo-Cuesta, S., Cediel, R., Moreno, A., Lorenzo-García, P. and Varela-Nieto, I. (2009). Design of a reverberant chamber for noise exposure experiments with small animals. Applied Acoustics, 70; 1034-1040.
Dalgaard, M., Hossaini, A., Hougaard, K., Hass, U. and Ladefoged, O. (2001). Developmental toxicity of toluene in male rats: effects on semen quality, testis morphology, and apoptotic neurodegeneration. Arch, 75; 103-109.
De Kloet, E.R., Joëls, M. and Holsboer, F. (2005). Stress and the brain: from adaptation to disease. Nat Rev Neurosci, 6; 463. 
Dobbs, M.R. (2009). Clinical Neurotoxicology E-Book: Syndromes, Substances, Environments. Elsevier Health Sciences, Kentucky, USA.  
Dolan, S. (2006). Stress, Self-Esteem, Health and Work, Palgrave Macmillan, London, UK.
Dorshkind, K. and Horseman, N.D. (2001). Anterior pituitary hormones, stress, and immune system homeostasis. BioEssays: news and reviews in molecular, cellular and developmental biology, 23; 288-294. 
Farzadinia, P., Bigdeli, M., Akbarzadeh, S., Mohammadi, M., Daneshi, A. and Bargahi, A. (2016). Effect of noise pollution on testicular tissue and hormonal assessment in rat. Andrologia, 48; 957-961.
Fathollahi, A., Jasemi, M. and Saki, G. (2013). Effect of noise stress on male rat fertility, and the protective effect of vitamins C and E on its potential effect. Arab J Urol, 11; 101-105.  
Folt, C., Chen, C., Moore, M. and Burnaford, J. (1999). Synergism and antagonism among multiple stressors. Limnol Oceanorg,44; 864-877. 
Gad, S.C. (2006). Animal models in toxicology, Second Edition. Taylor & Francis, Oxfordshire United Kingdom.
Gannouni, N., Mhamdi, A., El May, M., Tebourbi, O. and Rhouma, K.B. (2014). Morphological changes of adrenal gland and heart tissue after varying duration of noise exposure in adult rat. Noise and Health, 16; 416.
Gotohda, T., Tokunaga, I. and Kubo, S. I. (2005). Toluene inhalation-induced adrenocortical hypertrophy and endocrinological changes in rat. Life Sciences, 76; 1929-1937.
Haines, M.M., Stansfeld, S.A., Job, R.S., Berglund, B. and Head, J. (2001). Chronic aircraft noise exposure, stress responses, mental health and cognitive performance in school children. Psychol Med, 31; 265-277.
Heibati, B., Pollitt, K. J. G., Charati, J. Y., Ducatman, A., Shokrzadeh, M., Karimi, A. and Mohammadyan, M. (2018). Biomonitoring-based exposure assessment of benzene, toluene, ethylbenzene and xylene among workers at petroleum distribution facilities. Ecotoxicology and environmental safety, 149; 19-25.
IARC. (2020). IARC Monographs on the Identification of Carcinogenic Hazards to Humans. World Health Organization, International Agency for Research on Cancer. Volume 1-125. 
Ishigami, A., Tokunaga, I., Kubo S. I. and Gotohda, T. (2005). Immunohistochemical study of rat spermatogenesis after toluene-inhalation. Legal Med, 7; 42-46.
Jarup, L., Babisch, W., Houthuijs, D., Pershagen, G., Katsouyanni, K., Cadum, E., Dudley, M.L., Savigny, P., Seiffert, I. and Swart, W. (2008). Hypertension and exposure to noise near airports: the HYENA study. Environ Health Perspect, 116 (3); 329-333.
Kryter, K.D. (2013). Lee DHK, Hewson EW, Gurnham CF. The Effects of Noise on Man. Elsevier Science.
Lenzi, G. L. and Bonsanto, F. (2018). Air pollution and the nervous system: diseases of the brain caused by air pollutants and air pollution. Clinical handbook of air pollution-related diseases (pp. 263-302). Springer, Cham.  
Licitra, G., d’Amore, G. and Magnoni, M. (2018). Physical Agents in the Environment and Workplace: Noise and Vibrations, Electromagnetic Fields and Ionizing Radiation. CRC Press, USA.
Mader, K., Streffer, C., Bolt, H., Follesdal, D., Hall, P., Hengstler, J.G., Jacob, P., Oughton, D., Prieß, K. and Rehbinder, E. (2004). Low Dose Exposures in the Environment: Dose-Effect Relations and Risk Evaluation. Springer, Berlin, Heidelberg. 
Marti, O. and Armario, A. (1998). Anterior pituitary response to stress: time-related changes and adaptation. Int J Dev Neurosci, 16; 241-260. 
McQueen, C. (2010). Comprehensive Toxicology, Second Edition. Elsevier Science, Oxford, UK.
Monsefi, M., Bahoddini, A., Nazemi, S. and Dehghani, G. (2015). Effects of noise exposure on the volume of adrenal gland and serum levels of cortisol in rat. Iran J Med Sci, 31; 5-8.
Nakai, N., Murata, M., Nagahama, M., Hirase, T., Tanaka, M., Fujikawa, T., Nakao, N., Nakashima, K. and Kawanishi, S. (2003). Oxidative DNA damage induced by toluene is involved in its male reproductive toxicity, Free Radic Res, 37; 69-76.
Natelson, B.H. (2004). Stress, hormones and disease. Physiol. Behav, 82; 139-143.
Nicotera, T., Henderson, D., Zheng, X., Ding. D. and McFadden, S. (1999). Reactive oxygen species, apoptosis, and necrosis in noise-exposed cochleas of chinchillas. Abs Assoc Res Otolaryngol, 22; 159.
Oliveira, M.J., Monteiro, M., Ribeiro, A., Pignatelli, D. and Aguas, A. (2009). Chronic exposure of rats to occupational textile noise causes cytological changes in adrenal cortex. Noise and Health, 11; 118-123.
Ono, A., Kawashima, K., Sekita, K., Hirose, A., Ogawa, Y., Saito, M., Naito, K., Yasuhara, K., Kaneko, T., Furuya, T., Inoue, T. and Kurokawa, Y. )1999). Toluene inhalation induced epididymal sperm dysfunction in rats. Toxicology, 139; 193-205.
Piggott, J.J., Townsend, C.R. and Matthaei, C.D. (2015). Reconceptualizing synergism and antagonism among multiple stressors. Ecol Evol, 5; 1538-1547.
Prell, C.G.L., Henderson, D., Fay, R.R., Popper, A.N. (2011). Noise-Induced Hearing Loss: Scientific Advances. Springer, New York. 
Ranabir, S., Reetu, K. (2011). Stress and hormones. Indian J Endocr Metab,15; 18.
Redza-Dutordoir, M. and Averill-Bates, D.A. (2016). Activation of apoptosis signalling pathways by reactive oxygen species. BBA-GEN SUBJECTS- Mol Cell Res, 1863; 2977-2992.
Revilla, A.S., Pestana, C.R., Pardo-Andreu, G.L., Santos, A.C., Uyemura, S.A., Gonzales, M.E. and Curti, C. (2007). Potential toxicity of toluene and xylene evoked by mitochondrial uncoupling. Toxicol In Vitro, 21; 782-788.
Rider, C.V., Morata, T., Selgrade, M.K. and Sexton, K. (2018). Consideration of Physical Stressors in Cumulative Risk Assessment. Chemical Mixtures and Combined Chemical and Nonchemical Stressors. Springer; 467-492.
Rosenlund, M., Berglind, N., Pershagen, G., Järup, L. and Bluhm, G. (2001). Increased prevalence of hypertension in a population exposed to aircraft noise. Occup. Environ. Med, 58(12); 769-773.
Schäper, M., Seeber, A. and Van Thriel, C. (2008). The effects of toluene plus noise on hearing thresholds: an evaluation based on repeated measurements in the German printing industry, Int. J. Occup. Environ. Health. 21; 191-200.
Singh, M.P., Ravi Ram, K., Mishra, M., Shrivastava, M., Saxena, D.K. and Chowdhuri, D.K. (2010). Effects of co-exposure of benzene, toluene and xylene to Drosophila melanogaster: Alteration in hsp70, hsp60, hsp83, hsp26, ROS generation and oxidative stress markers. Chemosphere, 79; 577-587.
Stansfeld, S., Haines, M., Burr, M., Berry, B. and Lercher, P. (2000). A review of environmental noise and mental health. Noise and Health, 2(8); 1.
Taban, E., Mortazavi, S.B., Vosoughi, S., Khavanin, A. and Mahabadi, H.A. (2017). Noise Exposure Effects on Blood Glucose, Cortisol and Weight Changes in the Male Mice. Health Scope, 6(2).
Vlajkovic, S.M., Lin, S.C-y., Wong, A.C.Y., Wackrow, B., Thorne, P.R. (2013). Noise-induced changes in expression levels of NADPH oxidases in the cochlea. Hearing Res, 304:145-152.
Verma,Y. and Rana, S. (2008). Effects of progesterone on benzene toxicity in rats. Arh Hig Rada Toksikol, 1; 1-9.
Zidan, R.A. and Elnegris, H.M.. (2013). A histological study on the effect of noise on the adrenal cortex of adult male guinea pigs and the possible role of combined vitamins (A, C, and E) supplementation. Egypt J Histol, 36; 857-868.