-2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most widely used herbicides in the world, but its mutagenic and carcinogenic potential is still controversial. We simulated environmental exposure to 2,4-D, with the objective of evaluating the genotoxic effect of acute and chronic exposure to 2,4-D in rodents. We also evaluated the performance of machine learning algorithms in detecting differences in exposure groups through recognition performed from genotoxic characteristics. In the acute phase, 88 Swiss mice were used, distributed in five groups and exposed to nebulizations at different time intervals (24, 48, 72 and 192 hr). In the chronic phase, 88 Wistar rats were used, distributed in two groups (inhaled and oral) and exposed for six months. Femoral bone marrow cells were collected for a micronucleus test and comet assay. Data were evaluated by pattern recognition algorithms. In acute exposure, medium and high concentrations induced DNA damage in the comet assay, but these concentrations did not increase micronucleated cells. In the chronic exposure, there was an increase in micronuclei and DNA damage in the comet assay in all exposed groups regardless of the exposure route. The data showed a robust pattern of distinction between exposed and nonexposed groups to 2,4-D. Our data showed that both acute inhalation exposure and chronic oral and inhalation exposure to 2,4-D can cause genotoxic effects regardless of concentration. Machine learning showed a clear distinction between the control groups and those exposed to 2,4-D, and the effects of exposure are not concentration-dependent.
Glyphosate is the most widely used herbicide in the world. Although some studies have shown cardiac electrophysiological changes associated to glyphosate, the histopathological changes that this herbicide may cause in the cardiovascular system are not yet established. The aim of this study was to evaluate the cardiovascular effects of subchronic oral and inhalation exposure to the glyphosate herbicide in rats. Eighty albino Wistar rats were distributed into eight groups (five males and five females/group): inhalation control: nebulization with sodium chloride solution (NaCl); oral control: nebulized feed with NaCl; low inhalation concentration: nebulization with 3.71 × 10−3 grams of active ingredient per hectare (g.a.i./ha) of glyphosate; low oral concentration: nebulized feed with 3.71 × 10−3 g.a.i./ha of glyphosate; medium inhalation concentration: nebulization with 6.19 × 10−3 g.a.i./ha of glyphosate; medium oral concentration: nebulized feed with 6.19 × 10−3 g.a.i./ha of glyphosate; high inhalation concentration: nebulization with 9.28 × 10−3 g.a.i./ha of glyphosate; and high oral concentration: nebulized feed with 9.28 × 10−3 g.a.i./ha of glyphosate. After 75 days of exposure, the animals were euthanized, and aortas and hearts were collected for histopathological analysis. Fatty streaks were observed in most animals exposed to glyphosate and were more prevalent in male rats, regardless of the route of exposure ( p < 0.05). There were no differences in the measurements of the thickness of the right and left ventricle or in the collagen density of both ventricles in any of the groups evaluated ( p > 0.05). Our study suggests that glyphosate has atherogenic potential, regardless of the concentration and route of exposure.
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