Academic journal article Environmental Health Perspectives

Ultraviolet Photolysis of Chlorpyrifos: Developmental Neurotoxicity Modeled in PC 12 Cells

Academic journal article Environmental Health Perspectives

Ultraviolet Photolysis of Chlorpyrifos: Developmental Neurotoxicity Modeled in PC 12 Cells

Article excerpt

BACKGROUND: Ultraviolet photodegradation products from pesticides form both in the field and during water treatment.

OBJECTIVES: We evaluated the photolytic breakdown of the organophosphate pesticide chlorpyrifos (CPF) in terms of both the chemical entities generated by low-pressure ultraviolet C irradiation and their potential as developmental neurotoxicants.

METHODS: We separated by-products using high-performance liquid chromatography and characterized them by gas chromatography/mass spectrometry. We assessed neurotoxicity in neuronotypic PC12 cells, both in the undifferentiated state and during differentiation.

RESULTS: Photodegradation of CPF in methanol solution generated CPF oxon and trichloropyridinol, products known to retain developmental neurotoxicant actions, as well as a series of related organophosphate and phosphorothionate derivatives. Exposure conditions that led to 50% degradation of CPF thus did not reduce developmental neurotoxicity. The degradation mixture inhibited DNA synthesis in undifferentiated cells to the same extent as native CPF. In differentiating cells, the products likewise retained the full ability to elicit shortfalls in cell number and corresponding effects on cell growth and neurite formation. When the exposure was prolonged to the point where 70% of the CPF was degraded, the adverse effects on PC12 cells were no longer evident; however, these conditions were sufficiently severe to generate toxic products from the methanol vehicle.

CONCLUSIONS: Our results indicate that field conditions or remediation treatments that degrade a significant proportion of the CPF do not necessarily produce inactive products and, indeed, may elicit formation of even more toxic chemicals that are more water soluble and thus have greater field mobility than CPF itself.

KEY WORDS: chlorpyrifos, neurotoxicity, organophosphate insecticides, photolysis products, ultraviolet light. Environ Health Perspect 117:338-343 (2009). doi:10.1289/ehp.11592 available via http://dx.doi.org/ [Online 9 September 2008]

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The nearly ubiquitous exposure of the human population to organophosphate pesticides has raised increasing concern about their propensity to elicit developmental neurotoxicity at exposures that go undetected because of the absence of systemic signs of intoxication (Colborn 2006; Costa 2006; Landrigan 2001; Mileson et al. 1998; Slotkin 2005; Weiss et al. 2004). Chlorpyrifos (CPF), the most extensively studied of the organophosphates, disrupts neural cell replication and differentiation, axonogenesis, and synaptic function, culminating in behavioral deficits that have been noted both in animal models of developmental CPF treatment and in children in settings with high environmental CPF exposures (Rauh et al. 2006; Slotkin 1999, 2004, 2005). Although registration of CPF for use in the home has been withdrawn, it remains widely applied in agriculture, where issues remain about potential toxicity from runoff into natural water bodies and sources of drinking water or residues in food. In the field, CPF and other pesticides are exposed to conditions that lead to degradation, notably, photolysis from ultraviolet (UV) light. In water, these chemicals also can be degraded via environmental exposure to UV light and further transformed in water treatment processes. Recent studies of CPF photolytic products, CPF metabolites, and other organophosphates indicate that under these conditions, degradation involves the formation of a variety of known and unknown derivatives, some of which may retain developmental neurotoxicant features (Bavcon Kralj et al. 2007; Shemer and Linden 2006; Shemer et al. 2005).

In the present study, we evaluated the effects of different degrees of UVC irradiation of CPF and evaluated the potential neurotoxicity of the products in PC12 cells, a neurodevelopmental model derived from pheochromocytoma (Teng and Greene 1994) that recapitulates the major mechanisms and outcomes of CPF effects on the developing brain in vivo (Bagchi et al. …

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