Biomarkers of Chlorpyrifos Exposure and Effect in Egyptian Cotton Field Workers

Chlorpyrifos (CPF) belongs to the class of organophosphorus pesticides (OPs), which are the most commonly used pesticides worldwide. CPF produces neurotoxic effects via inhibition of β-esterases, including butyrylcholinesterase (BuChE), acetylcholinesterase (AChE), and carboxylesterase (reviewed by Costa 2006). The oxon metabolite of CPF mediates the inhibition of these β-esterases (Amitai et al. 1998). The inhibition of AChE is accepted as a primary mechanism by which OPs cause neurotoxicity. AChE inhibition increases acetylcholine in both central and peripheral cholinergic synapses, resulting initially in overstimulation of nicotinic and muscarinic receptors followed by receptor down-regulation. Acute cholinergic toxicity (OP poisoning) is generally thought to be mediated by overstimulation of receptors secondary to AChE inhibition, whereas it has been hypothesized that chronic OP neurotoxicity is due to receptor down-regulation (Costa 2006; Mileson et al. 1998). Although brain AChE cannot be practically monitored in humans exposed to CPF, red blood cell (RBC) AChE and plasma BuChE activities are used as biomarkers of effect both in the clinical setting (Thiermann et al. 2007) and the occupational setting (Quandt et al. 2010; Wilson et al. 2009). Plasma BuChE is more sensitive to OP exposure than RBC AChE (Amitai et al. 1998); therefore, BuChE is commonly used to monitor occupational exposure (Khan et al. 2008) and the response of acutely intoxicated individuals to oxime therapy (Aurbek et al. 2009; Wilson et al. 1997). Measuring cholinesterase (ChE) inhibition is a useful biomarker of OP exposure and effect, but it is not specific to CPF. 3,5,6-Trichloro-2-pyridinol (TCPy), a metabolite excreted in the urine, can be used as a specific biomarker of exposure of methyl and ethyl CPF (Barr et al. 2005). Analysis of urinary TCPy is useful in the occupational setting, as urine is one of the most common samples used for biological monitoring of OP exposure because of its abundance and ease of collection (Albers et al. 2004; Arcury et al. 2010; Barr et al. 1999; Hines and Deddens 2001; Steenland et al. 2000). TCPy concentration in the urine has also been used to assess CPF exposure in epidemiological studies of the general population (Whyatt et al. 2009). Although substantial data support the validity of urinary TCPy and blood ChE as biomarkers of exposure and effect after acute exposure to high concentrations of CPF, considerably less is known about their ability to predict adverse effects in populations exposed repeatedly to a range of CPF levels. Critical questions for which there are currently little directly relevant data include the relationship of blood ChE and urinary TCPy to exposure level and to each other after repeated occupational exposures. To address these questions, we quantified urinary TCPy levels and blood BuChE and AChE in a group of pesticide application workers in Menoufia Governorate, Egypt. Previous studies in Egyptian agricultural workers have shown that these workers have significant exposures to CPF (Farahat et al. 2010) and exhibit extensive neurobehavioral deficits compared with a control population (Abdel Rasoul et al. 2008; Farahat et al. 2003).