Difenoconazole (DIF) and dimethomorph (DIM) are widely used pesticides frequently detected together in environmental samples, so the deleterious effects of combined exposure warrant detailed examination. In this study, the individual and combined effects of DIM and DIF on conventional developmental parameters (hatching rate, deformity rate, lethality) and gene expression were measured in embryonic zebrafish. Both DIF and DIM interfered with normal zebrafish embryo development, and the most sensitive toxicity index for both was 96 h post-fertilization (hpf) deformity rate (BMDL₁₀ values of 0.30 and 1.10 mg/L, respectively). The combination of DIF and DIM had mainly synergistic deleterious effects on 96 hpf deformity and mortality rates. Transcriptome analysis showed that these compounds markedly downregulated expression of mcm family genes, cdk1, and cdc20, thereby potentially disrupting DNA replication and cell cycle progression. Enhanced surveillance for this pesticide combination is recommended as simultaneous environmental exposure may be substantially more harmful than exposure to either compound alone.

Growing evidence has revealed the deleterious influence of environmental and food contaminants on puberty onset and development in both animals and children, provoking an increasing health concern. T-2 toxin, a naturally-produced Type A trichothecene mycotoxin which is frequently found in cereal grains and products intended for human and animal consumption, has been shown to impair the reproduction and development in animals. Nevertheless, whether this trichothecene mycotoxin can disturb the onset of puberty in females remains unclear. To clarify this point, infantile female rats were given a daily intragastric administration of vehicle or 187.5 μg/kg body weight of T-2 toxin for five consecutive days from postnatal day 15 to 19, and the effects on puberty onset were evaluated in the present study. The results revealed that the days of vaginal opening, first dioestrus, and first estrus in regular estrous cycle were delayed following prepubertal exposure to T-2 toxin. The relative weights of reproductive organs uterus, ovaries, and vagina, and the incidence of corpora lutea were all diminished in T-2 toxin-treated rats. Serum levels of gonadotropins luteinizing hormone, follicle-stimulating hormone, and estradiol were also reduced by T-2 toxin treatment. The mRNA expressions of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary GnRH receptor displayed significant reductions following exposure to T-2 toxin, which were consistent with the changes of serum gonadotropins, delayed reproductive organ development, and delayed vaginal opening. In conclusion, the present study reveals that prepubertal exposure to T-2 toxin delays the onset of puberty in immature female rats, probably by the mechanism of disturbance of hypothalamic-pituitary-gonadal (HPG) axis function. Considering the vulnerability of developmental children to food contaminants and the relative high level of dietary intake of T-2 toxin in children, we think the findings of the present study provide valuable information for the health risk assessment in children.

Sulfur mustard (SM), a chemical warfare agent, can form adducts with DNA, RNA, and proteins. Reactions with DNA lead to the formation of both DNA monoadducts and interstrand cross-links, resulting in DNA damage, and is an important component of SM toxicity. Our previous in vivo studies indicated that dividing cells such as hematopoietic stem cells and intestinal villi stem cells seemed to have increased sensitivity to SM. Therefore, to compare the sensitivity of somatic and stem cells to SM and to investigate the mechanism of SM cytotoxicity, we isolated human foreskin fibroblasts, reprogrammed them into pluripotent stem cells, and then compared the DNA damage repair pathways involved upon SM treatment. Our results indicated that proliferating stem cells were more sensitive to SM-induced DNA damage, and the damage mainly comprised single-stranded breaks. Furthermore, the pathways involved in DNA repair in stem cells and somatic cells were different.

Unsymmetrical dimethylhydrazine (UDMH), a highly toxic rocket propellant with known multiorgan effects, requires urgent characterization of its chronic low‐dose toxicity. Using an integrated approach including exploratory transcriptomics ( n = 3/group) and metabolomic ( n = 4/group) approaches in male Sprague–Dawley rats exposed to high‐dose UDMH concentrations (100 ppm (v/v), 4 h/day, 5 days/week for 60 days), we delineated organ‐specific injury mechanisms and identified candidate systemic biomarkers. Histopathological assessment revealed significant pulmonary injury (62.5% incidence of focal hemorrhage, p = 0.015; inflammatory focus density: 8.3 ± 1.7 foci/mm ² ) and renal injury (tubular basophilia index: 1.8 ± 0.4, p < 0.001). Integrated multiomics analysis identified a mechanistically interconnected biomarker triad: (1) hepatic Cyp4a1 upregulation (log ₂ FC = 4.7), indicating PPARα‐mediated adaptive detoxification; (2) elevated serum taurine (1.27‐fold, p < 0.05), reflecting mitochondrial compensatory responses; and (3) increased urinary L‐DOPA (3.1‐fold, false discovery rate [FDR] < 0.05), signifying neuroendocrine dysregulation. Together, these core biomarkers delineate the pathophysiology of chronic UDMH toxicity, characterized by PPARα‐driven detoxification intersecting with mitochondrial stress adaptation and catecholaminergic disruption across organ systems. To our knowledge, this is the first integrated multiomics study of chronic UDMH exposure, establishing a mechanistic framework for toxicity and highlighting pulmonary–renal pathology, serum taurine, and hepatic Cyp4a1 as key indicators for developing future risk assessment strategies.