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Development Of A Risk Assessment Model For The Effects Of Organophosphorus Pesticides On Infectious Disease Susceptibility And The Immune System
Citation:
U.S. EPA. Development Of A Risk Assessment Model For The Effects Of Organophosphorus Pesticides On Infectious Disease Susceptibility And The Immune System.
Impact/Purpose:
The objectives of this project are to develop a model to provide data supporting improved integration of health and ecological risk assessment on the effects of organophosphorus pesticides on the immune system. For this model, environmental indicator species will be used to evaluate the effect of sublethal doses of pesticides, such as malathion, on immune function, and determine kinetics of cutaneous absorption to assess this as a primary route of exposure. The project phases are: 1) to determine if sublethal doses of an organophosphorus pesticide, malathion, are immunosuppresive to amphibians; and 2) to determine the rate of cutaneous absorption of a pesticide (malathion) which could cause adverse effects on the immune system. Properties of skin which are potential factors in the absorption of pesticides will be characterized using light and EM morphometry to measure overall skin thickness, epithelial cell length, epithelial layer number, intercellular pathway length, stratum corneum lipid layer patterns, glandular patterns, and distance to dermal vasculature at different body sites. Absorption kinetics of [14C]malathion across skin will then be measured using flow-through diffusion cells.
Description:
There is increased concern about the sublethal effects of organophosphorus (OP) pesticides on human and animal health. This class of chemicals has been shown to affect the immune function of macrophages and lymphocytes. Malathion, an OP compound, is one of the most widely used pesticides, applied to the environment at an annual rate of 4,486,000 in the US alone. While the most studied toxic effect of malathion is on cholinesterase in the nervous system, only a few studies have been conduced on its toxic effect on the immune system. A 1984 study observed that human occupationally exposed to OP compounds have marked impairment of neutrophil chemotaxis. These workers also had increased frequency of upper respiratory infections proportionate to the number of years of exposure to organophosphorus compounds. A 1983 study demonstrated a dose-response relationship to malathion induced chromosomal aberrations in mouse bone-marrow cells. A model was recently published in 1999 that demonstrated increased infectious disease susceptibility and mortality in amphibians externally exposed to field doses of an organophosphorus pesticide. Amphibians were selected as the model species for investigation because they are considered highly sensitive, environmental health indicator species that inhabit the aquatic and terrestrial interfaces. This research showed an increased susceptibility to bacterial infection in amphibians following pesticide exposure, strongly suggesting an effect on immune suppression that could correlate with reported effects in humans. For this next stage of research, environmental indicator species will be used to evaluate the effect of sublethal doses of pesticides, such as malathion, on immune function, and determine kinetics of cutaneous absorption to assess this as a primary route of exposure. The project phases are: 1) to determine if sublethal doses of an organophosphorus pesticide, malathion, are immunosuppresive to amphibians; and 2) to determine the rate of cutaneous absorption of a pesticide (malathion) which could cause adverse effects on the immune system. Willens S, Stoskopf MK, Baynes RE, Lewbart GA, Taylor SK, Kennedy-Stoskopf S. 2006. Percutaneous malathion absorption by anuran skin in flow-through diffusion cells. Environ Toxicol Pharmacol, 22(3):255-262. Willens S, Stoskopf MK, Baynes RE, Lewbart GA, Taylor SK, Kennedy-Stoskopf S. 2006. Percutaneous malathion absorption in the harvested perfused anuran pelvic limb. Environ Toxicol Pharmacol, 22(3):263-267.