T lymphocyte-proliferative responses of harbor seal (Phoca vitulina) peripheral blood mononuclear cells (PBMCs) exposed to pharmaceuticals in vitro

Highlights: • First study to measure toxicity of pharmaceuticals in marine mammal primary cells. • 17a-ethinyl estradiol, naproxen, erythromycin and carbamazepine suppressed harbor seal T cell proliferation. • Mixtures had non-additive effects on lymphocyte proliferation. • Male seal lymphocytes demonstrated a greater inhibition of proliferation to antibiotic erythromycin. - Abstract: The ubiquity of pharmaceuticals in the aquatic environment and the accumulation in organisms of lower trophic levels have been documented. The immunotoxicity of these xenobiotics has however been little investigated. This study assessed the effects of pharmaceuticals on the immune responses of harbor seal lymphocytes. Peripheral blood mononuclear cells isolated from harbor seal pups were exposed to varying concentrations of 17α-ethinyl estradiol (250–50,000 μg/L), naproxen (500–100,000 μg/L), carbamazepine (500–100,000 μg/L), erythromycin (750–150,000 μg/L) and binary mixtures thereof in vitro. All individual compounds and mixtures inhibited lymphocyte proliferation. Mixture effects were non-additive and predictive values overestimated the inhibition of proliferation. Male pups were more sensitive to erythromycin exposure. Comparison with the sensitivity of the 11B7501 cell line showed a higher sensitivity of pups to individual compounds and the inverse trend for mixtures. Based on our results, we hypothesize that pharmaceuticals may have the potential to interrupt immune functions in harbor seals.