Genotoxicity of imidacloprid in relation to metabolic activation and composition of the commercial product.
Imidacloprid is a neonicotinoid insecticide combining excellent efficiency against parasites with low toxicity for mammals. Commercially, it is co-formulated with dimethyl sulfoxide, methylpyrrolidone, propylene carbonate and mineral oil, which can modify its bioavailability and toxicological profile for humans following occupational exposure. A combined in vitro approach employing the comet assay and the micronucleus test was used to assess the genotoxicity of imidacloprid in relation to formulation, metabolic activation and exposure level. Human peripheral blood lymphocytes from unexposed healthy volunteers were treated with imidacloprid (0.2, 2 and 20 μM) and with equimolar concentrations of a commercial product, with and without addition of S9 fraction. Imidacloprid significantly increased the comet score and the frequency of micronuclei only at the highest concentration tested. DNA damage was slightly more severe with the commercial product, and was increased, though not significantly, by metabolic activation. Formation of reactive oxygen species (ROS) does not seem to be involved as a mechanism of genotoxicity, but this result may be explained by the insufficient sensitivity of the 2',7'-dichlorofluorescein diacetate assay at the test concentrations of imidacloprid. These results suggest that at concentrations<20 μM imidacloprid is not genotoxic to human lymphocytes in vitro. Nonetheless, the presence of co-formulants in the commercial product and occupational exposure, along with poor safety procedures, may present an increased risk for DNA fragmentation and chromosomal aberrations.
Costa
C
C
Dip. Medicina Sociale del Territorio, Sez. Medicina del Lavoro, Policlinico Universitario Gaetano Martino, 98125 Messina, Italy. ccosta@unime.it
Silvari
V
V
Melchini
A
A
Catania
S
S
Heffron
J J
JJ
Trovato
A
A
De Pasquale
R
R
D001682:Biological Availability; D002470:Cell Survival; D002869:Chromosome Aberrations / Q000187:drug effects; D020552:Comet Assay; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D019169:Jurkat Cells; D008214:Lymphocytes / Q000187:drug effects*; D015162:Micronucleus Tests / Q000379:methods; D008956:Models, Chemical; D009153:Mutagens / Q000633:toxicity*; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000633:toxicity*; D017382:Reactive Oxygen Species
D005609:Free Radicals; D007093:Imidazoles; D009153:Mutagens; D000073943:Neonicotinoids; D009574:Nitro Compounds; D017382:Reactive Oxygen Species; C082359:imidacloprid