Please cite this article in press as: Aguilar-Gardu ˜ no, C., et al., Changes in male hormone profile after occupational organophosphate exposure. A longitudinal study. Toxicology (2012), http://dx.doi.org/10.1016/j.tox.2012.11.001 ARTICLE IN PRESS G Model TOX-51101; No. of Pages 11 Toxicology xxx (2012) xxx–xxx Contents lists available at SciVerse ScienceDirect Toxicology jou rn al hom epage: www.elsevier.com/locate/toxicol Changes in male hormone profile after occupational organophosphate exposure. A longitudinal study C. Aguilar-Gardu ˜ no a,b , M. Lacasa ˜ na b,c,∗ , J. Blanco-Mu ˜ noz d , M. Rodríguez-Barranco c , A.F. Hernández e , S. Bassol f , B. González-Alzaga c , M.E. Cebrian g a Centre of Public Health Research (CSISP), Valencia, Spain b CIBER of Epidemiology and Public Health (CIBERESP), Spain c Andalusian School of Public Health, Granada, Spain d National Institute of Public Health, Cuernavaca, Morelos, Mexico e Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain f School of Medicine of Torreon, Autonomous University of Coahuila, Torreon, Mexico g Center for Research and Advanced Studies of the National Polytechnic Institute (IPN), Mexico, DF, Mexico a r t i c l e i n f o Article history: Received 30 May 2012 Received in revised form 29 October 2012 Accepted 1 November 2012 Available online xxx Keywords: Sex hormones Pesticides Endocrine system Occupational health Endocrine disrupting chemicals a b s t r a c t There is a growing concern about the endocrine effects of long-term, low-level exposure to organophos- phate (OP) compounds. Studies on experimental animals have found that OP pesticides have an impact on the endocrine system and a few clinical and epidemiological studies have also shown that OPs may affect the male hormone profile, although results are inconsistent. We have evaluated the effect of exposure to OP pesticides, measured through urinary levels of six dialkylphosphate (DAP) metabolites, on male hormone profile in 136 floriculture workers from the State of Mexico and Morelos during two agricul- tural periods with different degree of pesticide exposure. Generalized estimated equations (GEE) models were developed and adjusted for several potential confounders, including PON1 enzyme activity, as a biomarker of susceptibility, and serum levels of p,p  -DDE, a metabolite of the pesticide DDT widely used in Mexico until 1999 for control of agricultural pests and malaria. Exposure of male floriculture work- ers to OP pesticides was associated with increased serum levels of follicle-stimulating hormone (FSH) and prolactin and with decreased serum testosterone and inhibin B levels. Among all DAPs tested, only DETP was inversely associated with luteinizing hormone (LH). Estradiol showed a marginally significant positive trend with DEP and DETP derivatives. In conclusion, OP pesticides may have an impact on the endocrine function because of their potential to modify the male hormone profile as a function of the type of pesticide used as well as the magnitude of exposure. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Organophosphate (OP) pesticides are non-persistent com- pounds widely used for pest control at home or in agriculture activities. Workers employed in agriculture-related industries are at increased risk from pesticide exposure as confirmed by higher burdens of pesticide metabolites in biological samples in compar- ison to those found in subjects from non agricultural communities (Bouvier et al., 2005; Bradman et al., 2007; Cocker et al., 2002). Therefore, there is a growing concern about long-term, low-level exposure to OP compounds. ∗ Corresponding author at: Escuela Andaluza de Salud Pública, Campus Universi- tario de Cartuja, c/Cuesta del Observatorio 4, 18180 Granada, Spain. Tel.: +34 958 027556. E-mail address: marina.lacasana.easp@juntadeandalucia.es (M. Lacasa ˜ na). The acute adverse effects of OP on the central nervous sys- tem lies in the inhibition of acetylcholinesterase (AChE) at nerve endings, which leads to the accumulation of the neurotransmit- ter acetylcholine and consequently over-stimulation of muscarinic and nicotinic receptors (Bjørling-Poulsen et al., 2008; Ecobichon, 2001). However, little is known about chronic exposure to these chemicals, which has been associated with a number of health outcomes including neurocognitive effects (Baldi et al., 2001), neurodegenerative diseases (Franco et al., 2010), certain cancers (Bonner et al., 2010), adverse reproductive effects (Moreno-Banda et al., 2009; Peiris-John and Wickremasinghe, 2008), respiratory effects (Hernández et al., 2011) and endocrine disruption (Blanco- Mu˜ noz et al., 2010; Lacasa ˜ na et al., 2010; Meeker et al., 2006). Experimental studies have shown that OP can act as endocrine disrupting chemicals (EDC) because of their capacity to impair the male sexual hormone profile (Kang et al., 2004; Rattner et al., 1986; Sarkar et al., 2000). Furthermore, clinical and epidemiological stud- ies conducted in men with environmental or occupational exposure 0300-483X/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tox.2012.11.001