Chloro-s-triazines-toxicokinetic, Toxicodynamic, Human Exposure, and Regulatory Considerations

Abstract

Chloro-s-triazines-atrazine, cyanazine, propazine, simazine, and terbuthylazine-are structurally similar herbicides, differing only in specific s-triazine4-and 6-N alkyl substituents. It is generally regarded that their toxicokinetics, such as, metabolic pathways, biological effects and toxicities, also share more similar features than the differences. Consequently, it is useful to compare their characteristics to potentially find useful structure-activity relationships or other similarities or differences regarding different active compounds, their metabolites, and biological effects including toxic outcomes. The ultimate goal of these exercises is to apply the summarized knowledge-as far as it is possible regarding a patchy and often inadequate database-to cross the in vitro-in vivo and animal-human borders and integrate the available data to enhance toxicological risk assessment for the benefit of humans and ecosystems.

Keywords: Chloro-s-triazines; biotransformation; human exposure; metabolites; regulatory guidance.; toxicity.

Fig. (1)

Consensus metabolic map of chloro-s-triazines in mammals (modified from EFSA PPR Panel [6]).

Fig. (2)

CYP mRNA induction levels in the human hepatoma cell line HepaRG after incubation for 24 h with DMSO (control cells), atrazine, and model inducers: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (AHR agonist and CYP1A2 model inducer), phenobarbital (PB) (CAR activator and CYP2A6 and CYP2B6 inducer), rifampicin (RF) (PXR agonist and CYP3A4 inducer), or DMSO (control cells). CYP1A2, CYP2A6, CYP2B6 or CYP3A4 mRNA levels were measured by TaqMan probes using RT-PCR analysis. The mRNA levels were expressed relatively to those in control cells (considered as 1) and data are expressed as mean ± SD of six replicates (data from Abass et al. [36]). (A higher resolution version of this figure is available in the electronic copy of the article).