Ecotoxicological evaluation of carbamazepine using six different model systems with eighteen endpoints.
The occurrence of pharmaceutically active compounds in the aquatic environment has been recognized as one of the emerging issues in environmental chemistry. However, the ecotoxicological effects of pharmaceuticals have still not been researched adequately. Carbamazepine, an anticonvulsant commonly present in surface and groundwater, was studied, using six ecotoxicological model systems with eighteen endpoints evaluated at different exposure time periods. The battery included the immobilization of Daphnia magna, bioluminescence inhibition in the bacterium Vibrio fischeri, growth inhibition of the alga Chlorella vulgaris, and micronuclei induction and root growth inhibition in the plant Allium cepa. Cell morphology, neutral red uptake, total protein content, MTS metabolization, lactate dehydrogenase leakage and activity and glucose-6-phosphate dehydrogenase activity were studied in the salmonid fish cell line RTG-2. The total protein content, LDH activity, neutral red uptake and MTT metabolization in Vero monkey kidney cells were also investigated. The most sensitive system to carbamazepine was the Vero cell line, followed by Chlorella vulgaris, Vibrio fischeri, Daphnia magna, Allium cepa, and RTG-2 cells. EC50 values from 19 microM in Vero cells at 72 h to more than 1200 microM in other systems, were obtained. Comparing the concentrations in water and the toxicity quantified in our assay systems, carbamazepine is not expected to produce acute toxic effects in the aquatic biota under these circumstances, but chronic and synergistic effects with other chemicals cannot be excluded.
National Institute of Toxicology, PO Box 863, 41080-Sevilla, Spain.
A
A
Jos
G
G
Repetto
J C
JC
Rios
M J
MJ
Hazen
M L
ML
Molero
A
A
del Peso
M
M
Salguero
P
P
Fernández-Freire
J M
JM
Pérez-Martín
A
A
Cameán
D023401:Animal Use Alternatives; D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis; D002220:Carbamazepine / Q000633:toxicity*; D002460:Cell Line; D002708:Chlorella / Q000187:drug effects / Q000254:growth & development; D002522:Chlorocebus aethiops; D003621:Daphnia / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D017753:Ecosystem; D023381:Endpoint Determination / Q000379:methods*; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D017686:Oncorhynchus mykiss; D019697:Onions / Q000187:drug effects / Q000235:genetics; D018675:Toxicity Tests / Q000379:methods*; D014709:Vero Cells; D014733:Vibrio / Q000187:drug effects / Q000502:physiology; D014874:Water Pollutants, Chemical / Q000633:toxicity
D000927:Anticonvulsants; D015415:Biomarkers; D014874:Water Pollutants, Chemical; D002220:Carbamazepine