Evaluation of flubendiamide toxicity through one generation extended reproductive study in rats
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Date
2016-03-01
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GADVASU, Ludhiana
Abstract
The present study was planned to investigate the effect of flubendiamide on Balb/c fibroblast cell culture and rats of either sex belonging to Sprague dawley stock. Initial testing of flubendiamide in fibroblast culture revealed IC50 of 68.1 µg.ml-1 translating to a theoretical LD50 of 508.08 mg.kg-1 body weight which served as the starting dose for acute toxicity studies. A preliminary trial of 28 days was carried out (at the dose rate of 0, 125, 250, 500 and 1000 mg.kg-1) to arrive at MTD of 250 mg.kg-1 on the basis of body weight reduction compared to control. There was significant alteration in relative organ weight (heart, liver, kidney, testes and uterus with ovary) and biochemical (AST, ALT, LDH, ALP, GGT, glucose and BUN), hematological (TLC, TEC, PCV, MPV and platelet count), antioxidant (CAT, GPx, GST, LPO, GSH, GR and G6PD) and hormonal (T3) parameters. Further testing of parent generation (0, 2, 10, 50 and 250 mg.kg-1) was carried out at derived doses. Significant changes were observed in body weight from 610 weeks in males, relative organ weight (kidney and brain) and biochemical (ALP, direct bilirubin, GGT, cholesterol, creatinine, CK, Na+, total bilirubin, K+ and SGPT), hematological (TEC, PCV, MCV, MCH, MCHC, platelet count and MPV), antioxidant (GSH and G6PD) and hormonal (T3, T4 and insulin) parameters. In addition significant reduction in sperm count and resultant reduced number of pregnancies compared to control was noted. F1 generation rats were divided randomly into two subsets for neuroimmune (PND 63) and reproductive testing (PND 84). In F1 generation rats, no significant changes in body weight were observed. In the neuro-immune subset significant changes in biochemical (BUN, Ca2+, cholesterol, Mg2+, phosphorus, SGOT, CK, GGT, SGPT and Na+) and hematological (TLC and MCHC) parameters were observed. Increase in time spent in locomotion, reduced sleeping time with damage to brain through histopathological examination revealed congestion and necrosis of glial cells and astrocytes. No significant change in HA titre, paw swelling or stimulation indices (LPS and Concanavalin A) was observed but loss of white pulp in spleen could be seen histopathologically. In reproductive subset dosing was continued till sacrifice (PND 84). In reproductive subset significant changes in biochemical (albumin, BUN, Ca2+, creatinine, GGT, glucose, LDH, Mg2+, K+, Na+, SGOT, SGPT, phosphorus, total bilirubin and total protein), hematological (TEC, Hb, PCV, MCHC, MPV and platelet count) and hormonal (T3, T4 and insulin) parameters was observed. Non linear increase in toxicity with increase in dose rate was observed and toxicity varied with sex as well. The present study concludes the pesticide to be toxic to reproductive, immune and nervous system at different dose levels.
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