Qiu_2026_Pestic.Biochem.Physiol_216_106750

Although fosthiazate (FOS) is a novel chiral organophosphorus nematicide, its enantioselective toxicity to Bombyx mori remains inadequately characterized. This study systematically evaluated the acute and developmental toxicity of FOS stereoisomers by determining LC(50) values and assessing enzyme activity, oxidative stress biomarkers, growth metrics, and silk gland histopathology. Acute toxicity assays revealed profound stereoselectivity; specifically, (1S,3R)-fosthiazate (SR-FOS) and (1S,3S)-fosthiazate (SS-FOS) exhibited toxicity more than 10-fold higher than the other stereoisomers. Following sublethal exposure (8.54 mg/L), SR-FOS and SS-FOS significantly inhibited acetylcholinesterase (AChE) activity, upregulated the expression of ace1 and ace2 genes by 2.46- to 7.35-fold, and induced severe oxidative stress, marked by a 38.02-62.61 % increase in ROS, a 28.75-65.18 % increase in SOD activity, a 34.96-110.93 % increase in CAT activity, and a 1.91- to 3.88-fold elevation in MDA levels. In addition, developmental toxicity also varied significantly among stereoisomers. SR-FOS and SS-FOS reduced pupal weight by 16.82-17.76 % and cocoon shell weight by 21.88-28.13 %. These stereoisomers also caused severe damage to the silk glands, accompanied by a 1.21- to 6.45-fold downregulation of genes encoding fibroin (Fib-H, Fib-L), sericin (Ser1, Ser2, Ser3), and the silk gland factor 1 (SGF1), indicating that disrupted silk synthesis is a key mechanism of chronic toxicity. Furthermore, UPLC-MS/MS results showed that the residues of the four stereoisomers in silkworm excrement also showed significant differences (RS/RR-FOS > SR/SS-FOS). These findings establish critical structure-activity relationships for FOS, which are essential for the risk assessment of chiral pesticides.