Effect of atrazine and fenitrothion at no-observed-effect-levels (NOEL) on amphibian and mammalian corticosterone-binding-globulin (CBG)

[Display omitted] •The study determines NOEL atrazine/fenitrothion effect on amphibian/mammal CBG.•Atrazine/fenitrothion compete with B for binding CBG in cane toad and rat plasma.•Atrazine NOEL would interfere with normal B-CBG interaction in amphibian.•Displacement of B by the agrochemicals would affect total:free B in plasma.•Increase of free B will lead to an indirect disruption to stress response. This study determines the effect of atrazine and fenitrothion no-observed-effect-levels (NOEL) on the binding of corticosterone (B) to corticosterone-binding-globulin (CBG) in an amphibian and a mammal. Plasma from five cane toads and five Wistar rats was exposed to atrazine and fenitrothion at the NOEL approved for Australian fresh water residues and by the World Health Organization (WHO). The concentration required to displace 50% (IC50) of B binding to CBG was determined by a competitive microdialysis protein assay. Competition studies showed that both atrazine and fenitrothion at NOEL are able to compete with B for CBG binding sites in toad and rat plasma. The IC50 levels for atrazine in toads and rats were 0.004nmol/l and 0.09nmol/l respectively. In the case of fenitrothion the IC50 level found in toads was 0.007nmol/l, and 0.025nmol/l in rats. Plasma dilution curves showed parallelism with the curve of B, demonstrating that these agro-chemicals are competitively inhibiting binding to CBG. The displacement of B by atrazine and fenitrothion would affect the total:free ratio of B and consequently disrupt the normal stress response. This is the first time that the potential disruptive effect of atrazine and fenitrothion on B-CBG interaction at the NOELs has been demonstrated in amphibian and mammalian models.