MP2 Toxicity of Mixtures
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() Mixtures of organochlorines modulate B and T lymphocyte proliferation in marine mammals and mice.

Mori, C1, Morsey, B1, Levin, M1, De Guise, S1, 1 Univesity of Connecticut, Storrs, CT, USA

ABSTRACT- Marine mammals, being long-lived and on top of the food chain, biomagnify and bioaccumulate environmental contaminants such as organochlorines (OCs). The effects of anthropogenic compounds on the immune system have been studied, however, relatively little is known about the immunomodulatory effects of chemicals in mixtures. This study focused on species differences in the response to the immunomodulatory effects of OCs and determined OC interaction in mixtures. Five OCs consisting of four PCB congeners, PCB IUPAC #138, 153, 169, and 180, as well as 2,3,7,8-TCDD and all possible combinations (26) were tested upon in vitro exposure. B6C3F1 mice were always tested in parallel to marine mammals for quality control and comparison with marine mammals. Con A-induced T cell proliferation was modulated in all nine species tested. LPS-induced B cell proliferation was modulated in two out of four species tested. There were qualitative and quantitative differences in mixtures modulating immune functions in different species, with evidence for additive, synergistic and antagonistic interactions. Additionally, TEQ (toxic equivalent) values, derived from the estimate toxicity of a compound relative to TCDD, did not predict immunotoxicity of OCs in any of the species tested. Thus, our results demonstrate important differences between species, and that the commonly used mouse model utilized for predicting immunotoxicity in other species may not be appropriate to determine the risk associated with exposure to mixtures of OCs. Furthermore, the effects of a mixture of chemicals cannot always be predicted from that of its components nor from the TEQ values, which will complicate risk assessment. Testing these immunomodulatory effects of chemical mixtures in different species should aid in the risk assessment as well as global conservation and management strategies of the overall anthropogenic effects on marine mammal populations.

Key words: organochlorines, mixtures, immunotoxicology, marine mammals

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