The following post is by Gamola Fortenberry, one of our 2012 Risk Science Fellows, Gamola has an MPH in Environmental Quality and is a PhD candidate in the Department of Environmental Health Science. You can read more about her research project here
In the U.S., pesticide expenditures in 2007 accounted for 32% of the world’s total pesticide spending and 39% for insecticides, specifically, with agriculture and home/garden accounting for 46 and 38% of insecticide usage, respectively (U.S. EPA, 2011) . Most occurrences of human pesticide exposure are at low levels that do not typically elicit a biological response; however, some studies have shown that low levels of exposure are associated with health outcomes such as adverse neurodevelopment in children.
Of the numerous pesticides in use in the U.S., I’m most interested in chlorpyrifos, an organophosphate, insecticide, which was banned for residential use in 2000 but is actively used agriculturally in the U.S with approximately 10 million pounds applied annually in the U.S. (U.S. EPA, 2011). Globally, chlorpyrifos is the most widely used non-persistent, organophosphate (OP) residentially and agriculturally and is registered for use in over 100 countries. Registered use sites include the following: food crops, including fruit and nut trees, many types of fruits and vegetables, and grain crops; and non-food crops such as forage, golf course turf, industrial sites, greenhouse and nursery production, sod farms, and wood products. Public health uses include aerial and ground-based fogger treatments to control mosquitoes (U.S. EPA, 2011). Particularly in Mexico, organophosphates are widely used for animal husbandry, alfalfa, and crops for animal feed production (Salas et al., 2003) and may be a significant source for human chlorpyrifos, chlorpyrifos-methyl, or TCPY (a specific metabolite of chlorpyrifos and chlorpyrifos-methyl) exposure.
Environmental human exposure to chlorpyrifos, chlorpyrifos-methyl, and their metabolite TCPY are ubiquitous and occurs through inhalation of vapors and aerosols from spray drift, ingestion of residuals on food and house dust/, and dermal absorption following skin contact (Panuwet et al. 2008). Inhalation of indoor air also plays a role in chlorpyrifos, chlorpyrifos-methyl, or TCPY exposure as the indoor half-life is several months due to lack of degradation sources such as sunlight, water, and/or soil microorganisms in carpet dusts while the biological half-life is 27 hours. Maternal chlorpyrifos, chlorpyrifos-methyl, and TCPY exposure serves as a source of fetal exposure due to passage through the blood-brain barrier, placenta, and amniotic fluid.
Chlorpyrifos has been the source of much controversy regarding health impacts and its continued use. Human and experimental studies have shown that fetuses and infants are more sensitive than adults to many environmental toxicants including chlorpyrifos (Timchalk et al, 2007) and these exposures impact fetal growth and early childhood neurodevelopment (F. P. Perera et al., 2005; Eskenazi et al., 2007; Rauh et al., 2006; Engel et al., 2011). Several animal studies have demonstrated that gestational and/or postnatal exposures to chlopyrifos, chlorpyrifos-methyl, and TCPY induce neurobehavioral alterations, especially at doses that inhibit acetylcholinesterase (AChE) activity (De Angelis et al., 2009). As a result, behavioral changes such as hyperactivity and memory errors occur (Eaton et al., 2008). However, studies have also shown that OPs at doses that cause only minimal AChE inhibition may also disrupt fetal brain development, neurobehavioral and cognitive outcomes through noncholinergic mechanisms (Rauh et al., 2006; Garcia, Seidler, & Slotkin, 2003; Eskenazi et al., 2008; F. P. Perera et al., 2005).
This summer, I will be working with the Early Life Exposure in Mexico to Environmental Toxicant (ELEMENT) population. This is population is composed of several cohorts of pregnant women based in Mexico City, Mexico. Within these cohorts, I will examine prenatal chlorpyrifos, chlorpyrifos-methyl, or TCPY exposure in relation to neurodevelopment in childhood using TCPY as a biomarker of exposure. I’m excited that the Risk Science Center has seen the value and importance of this research and cannot wait to share my findings with the rest of the fellows and faculty in the Fall.
- De Angelis, S., Tassinari, R., Maranghi, F., Eusepi, A., Di Virgilio, A., Chiarotti, F., Mantovani, A. (2009). Developmental exposure to chlorpyrifos induces alterations in thyroid and thyroid hormone levels without other toxicity signs in CD-1 mice. Toxicological Sciences, 108(2), 311-319.
- Eaton, D., Daroff, R., Autrup, H., Bridges, J., Buffler, P., Costa, L., Spencer, P. (2008). Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment. Critical Reviews in Toxicology, 38 Suppl 2, 1-125.
- Engel, S. M., Wetmur, J., Chen, J., Zhu, C., Barr, D. B., Canfield, R. L., & Wolff, M. S. (2011). Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Environ Health Perspect, 119(8)
- Eskenazi, B., Marks, A., Bradman, A., Harley, K., Barr, D., Johnson, C., Jewell, N. (2007). Organophosphate pesticide exposure and neurodevelopment in young mexican-american children. Environmental Health Perspectives, 115(5), 792-798.
- Eskenazi, B., Rosas, L., Marks, A., Bradman, A., Harley, K., Holland, N., Barr, D. (2008). Pesticide toxicity and the developing brain. Basic Clinical Pharmacology Toxicology, 102(2), 228.
- Garcia, S., Seidler, F., & Slotkin, T. (2003). Developmental neurotoxicity elicited by prenatal or postnatal chlorpyrifos exposure: Effects on neurospecific proteins indicate changing vulnerabilities. Environmental Health Perspectives, 111(3), 297-303.
- Panuwet, P., Prapamontol, T., Chantara, S., Thavornyuthikarn, P., Montesano, M. A., Whitehead, R., & Barr, D. (2008). Concentrations of urinary pesticide metabolites in small-scale farmers in chiang mai province, thailand. The Science of the Total Environment, 407(1), 655-668.
- Perera, F. P., Rauh, V., Whyatt, R. M., Tang, D., Tsai, W. Y., Bernert, J. T., Kinney, P. L. (2005). A summary of recent findings on birth outcomes and developmental effects of prenatal ETS, PAH, and pesticide exposures. Neurotoxicology, 26(4), 573-587.
- Rauh, V., Garfinkel, R., Perera, F., Andrews, H., Hoepner, L., Barr, D., Whyatt, R. (2006). Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics, 118(6), e1845-e1859.
- Salas, J., Gonzlez, M., Noa, M., Prez, N., Daz, G., Gutirrez, R., Osuna, I. (2003). Organophosphorus pesticide residues in mexican commercial pasteurized milk. Journal of Agricultural and Food Chemistry, 51(15), 4468-4471.
- Timchalk, C., Busby, A., Campbell, J., Needham, L., & Barr, D. (2007). Comparative pharmacokinetics of the organophosphorus insecticide chlorpyrifos and its major metabolites diethylphosphate, diethylthiophosphate and 3,5,6-trichloro-2-pyridinol in the rat. Toxicology, 237(1-3), 145.
- U.S. Environmental Protection Agency (2011). Chlorpyrifos Facts. http://www.epa.gov/oppsrrd1/REDs/factsheets/chlorpyrifos_fs.htm. Accessed August 18, 2011.
U.S. Environmental Protection Agency (2011). Pesticides Industry Sales and Usage: 2006 and 2007 Market Estimates. http http://www.epa.gov/opp00001/pestsales/07pestsales/market_estimates2007.pdf. Accessed March 10, 2012.