Review of the pharmacokinetics and metabolism of triclopyr herbicide in mammals: Impact on safety assessments

Architecture and potential roles of a delta-class glutathione S-transferase in protecting honey bee from agrochemicals

“…Of the ligands screened, TCP was found to be the tightest binder with a K i = 25.04 μM (Table 4). In addition to being a metabolite of the herbicide triclopyr, TCP is also the hydrolysis product of the organophosphate chlorpyriphos (Bartels et al, 2020;Jeon et al, 2023). In our study, TCP was the only compound able to displace more than 50% of ANS from AmGSTD1.…”

Comparative hepatotoxicity of a herbicide, epyrifenacil, in humans and rodents by comparing the dynamics and kinetics of its causal metabolite

“…31,32) Furthermore, it has been reported that there are species differences in the active transport of chemicals and thereby species differences in exposure and toxicity. [33][34][35] When considering the target organs of epyrifenacil, the active transport is mainly contributed to the liver rather than the hemopoietic system, and thus we focused on evaluating species differences in the hepatic uptake of S-3100-CA. The results of in vitro assays using hepatocytes from rodents and humans demonstrated that the uptake of S-3100-CA is 6 to 13 times greater in mice and 2 times greater in rats than in humans.…”

Opportunities and challenges related to saturation of toxicokinetic processes: Implications for risk assessment

“…This simulation study also brings to light an issue regarding common approaches used to estimate a KMD by evaluating the degree of disproportionality of systemic exposure to administered dose. These approaches include visual inspection of the administered dose versus systemic exposure data, comparison of fold changes in administered doses and systemic exposures ( Loccisano et al, 2020 ; Saghir et al, 2013 ; Terry et al, 2014 ), and statistical methods to determine if any of the data points deviate from the linear assumption ( Bartels et al, 2020a , 2020b ; McFadden et al, 2012 ; Saghir et al, 2012 ). All these approaches are based on the premise that a KMD is the onset (or an inflection point) of nonlinear TK, but as shown in our case study, systemic exposure can deviate from proportionality starting at very low administered dose ( Fig.…”

“…While variations of the KMD approach have been applied in several studies ( Bartels et al, 2020a , 2020b ; Borghoff et al, 2016 ; Loccisano et al, 2020 ; Saghir et al, 2012 ; Van Cott et al, 2018 ), there is no consensus on how a KMD should be estimated or when such an approach is appropriate. The lack of consensus is partly due to the vague definition of a KMD, which refers to an inflection point that signals the onset of nonlinear TK behavior ( McFadden et al, 2012 ; Saghir, 2015 ; Saghir et al, 2013 ).…”