Gul Sahika Gokdemir, Mehmet Cihan Yavaş, Selim Demirtaş, Fazile Cantürk Tan, Salih Varol, Mehmet Tahir Gokdemir
{"title":"Dose-Related Gastric Toxicity of Diethyl Phthalate in Female Wistar Rats.","authors":"Gul Sahika Gokdemir, Mehmet Cihan Yavaş, Selim Demirtaş, Fazile Cantürk Tan, Salih Varol, Mehmet Tahir Gokdemir","doi":"10.1002/jat.70445","DOIUrl":"10.1002/jat.70445","url":null,"abstract":"<p><p>Diethyl phthalate (DEP) is commonly used in cosmetics, personal care products, and pharmaceutical formulations as a low-molecular-weight phthalate. Despite its widespread use, information on its effects on the gastric mucosa remains limited. This study examined the dose-related effects of DEP on inflammation, oxidative stress, gastric mucosal defense, DNA damage, apoptosis, and histopathological changes in rat gastric tissue. Twenty-eight female Wistar rats were randomly assigned to four groups (n = 7 per group): control and DEP (100, 300, or 600 mg/kg/day). These experimental toxicological doses were administered by oral gavage for 21 days. Gastric tissue levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), superoxide dismutase (SOD), malondialdehyde (MDA), trefoil factor family 1 (TFF1), and mucin-5AC (MUC5AC) were determined by ELISA. Histopathological examination, Bax/Bcl-2 immunohistochemistry, and comet assay were performed. Dose-response relationships were assessed using polynomial trend analysis. DEP exposure resulted in significant dose-dependent increases in IL-6, TNF-α, COX-2, MDA, Bax expression, Bax/Bcl-2 ratio, histopathological damage, and DNA damage (all p < 0.001), whereas SOD levels and Bcl-2 expression significantly decreased (all p < 0.001). TFF1 and MUC5AC levels were significantly increased at 100 mg/kg but significantly decreased at 600 mg/kg compared with controls. Histopathological examination showed progressive gastric mucosal injury with increasing DEP doses. DEP exposure induced dose-related changes in gastric inflammation, oxidative stress, mucosal protective factors, histopathology, DNA damage, and apoptosis-related protein expression. The findings suggest that oxidative stress and inflammation are associated with altered mucosal defense, DNA damage, and apoptosis following DEP exposure.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4242-4254"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fernando Ferreira da Cunha Filho, Alex Souza Moraes, João Paulo Siqueira da Silva, Edvane Borges da Silva, Ademir Amaral, André Maciel Netto
{"title":"Human Health Risk Assessment From Exposure to Toxic Metals in Soils and Leafy Vegetables in Smallholder Farms of Northeastern Brazil.","authors":"Fernando Ferreira da Cunha Filho, Alex Souza Moraes, João Paulo Siqueira da Silva, Edvane Borges da Silva, Ademir Amaral, André Maciel Netto","doi":"10.1002/jat.70164","DOIUrl":"10.1002/jat.70164","url":null,"abstract":"<p><p>This study assessed human health risks associated with exposure to potentially toxic metals (PTMs) in soils and leafy vegetables cultivated in smallholder agricultural systems in Northeastern Brazil. Soil and vegetable samples were collected from 18 agricultural areas and analyzed for cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), nickel (Ni), lead (Pb), and zinc (Zn). A harmonized human health risk assessment (HHRA) was conducted following US Environmental Protection Agency (USEPA) guidelines, considering soil ingestion, dermal contact, inhalation of resuspended particles, and dietary intake of vegetables for adults and children. Recalculated average daily doses indicated that soil ingestion and vegetable consumption were the dominant exposure pathways, whereas dermal and inhalation contributions were minor. Children consistently exhibited higher exposure doses and hazard quotients than adults due to lower body weight and higher intake rates. Noncarcinogenic risk estimates for adults remained below the threshold of concern in all areas. In contrast, localized exceedances of the hazard index (HI > 1) were identified for children, revealing spatially explicit risk hotspots rather than uniform risk across the study area. Lettuce and arugula contributed substantially to dietary exposure, particularly for Cd, Pb, and Cr. A conceptual sensitivity analysis incorporating hypothetical bioaccessibility fractions demonstrated that risk estimates near the regulatory threshold are sensitive to realistic reductions in bioaccessible metal fractions. At the same time, the highest risk hotspots remain robust under conservative assumptions. Overall, the findings represent conservative, screening-level estimates that underscore the importance of age-specific exposure scenarios, spatially explicit risk evaluation, and targeted risk management strategies in smallholder farming systems.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"3989-3999"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ying Zhang, Jinjin Zhao, Tao Huang, Xiaocheng Gao, Lan Zhang, Yanhong Wang, Xinyue Guo, Ling Zhang, Qiao Niu, Qinli Zhang
{"title":"Vps34 Knockdown Alleviated the Long-Term Effect of Nano-Alumina on Cognitive Impairment in Zebrafish When in Embryos.","authors":"Ying Zhang, Jinjin Zhao, Tao Huang, Xiaocheng Gao, Lan Zhang, Yanhong Wang, Xinyue Guo, Ling Zhang, Qiao Niu, Qinli Zhang","doi":"10.1002/jat.70186","DOIUrl":"10.1002/jat.70186","url":null,"abstract":"<p><p>Nano-alumina (AlNPs) exposure induced learning and memory impairment, which was associated with over-activation of mitophagy. Our previous study found that reduction of Vacuolar Protein Sorting 34 (Vps34), a core initiating gene for autophagy, alleviated AlNPs-exposed neurodevelopmental toxicity, so we hypothesized that Vps34 knockdown may mitigate the damage to learning and memory induced by AlNPs. This study aimed to investigate the effects and mechanisms of Vps34 knockdown on the long-term cognitive impairment of AlNPs in the zebrafish brain. A 500 μL of morpholino oligonucleotide at 1 mmol/L was microinjected into embryos within 1 h postfertilization (hpf). These embryos and control embryos were randomly assigned to control, negative control, Vps34 knockdown, AlNPs exposure (100 mg/L), and AlNPs exposure with Vps34 knockdown up to 144 hpf. After zebrafish were given to brine shrimp and E3 medium up to 6 months, their locomotor activity and cognitive behavior were assessed. Meanwhile, we investigated brain structure, oxidative stress, mitochondria, and mitophagy. Our results indicated that AlNPs exposure with Vps34 knockdown significantly enhanced the average speed, moving distance, time spent in the outer zone, and cumulative time in the T-maze while decreasing latency in the T-maze compared with the AlNPs-exposed group. Moreover, AlNPs exposure with Vps34 knockdown increased the number of neurons while lowering the mitophagosome in the brain compared with exposure to AlNPs. Then, AlNPs exposure with Vps34 knockdown enhanced higher activities of superoxide dismutase (SOD), Na<sup>+</sup>-K<sup>+</sup>ATPase and Ca<sup>2+</sup>-Mg<sup>2+</sup>ATPase, and levels of mitochondrial membrane potential (MMP) and translocase of outer mitochondrial membrane 20 (TOMM20) protein, while decreasing activities of reactive oxygen species (ROS) and lactate dehydrogenase (LDH), and levels of microtubule-associated protein 1 light chain 3 (LC3II) and translation of the inner member (TIM23) protein compared with AlNPs exposure. At last, AlNPs exposure significantly increased the abundances of the Vps34 and PTEN-induced putative kinase 1 (PINK1) mRNA in the brain compared with the control and AlNPs exposure with Vps34 knockdown groups. Therefore, inhibiting Vps34 protected against the cognitive impairment caused by AlNPs exposure by reducing mitophagy and restoring mitochondrial structure and function.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4186-4198"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahmood Ahmed, Faryal Chaudhry, Anum Khaleeq, Arslan Usman, Zoya Sohail, Mahrukh Faisal, Khairia Mohammed Al-Ahmary, Muhammad Zubair, Masooma Irfan, Ali Abbas Aslam
{"title":"Human Exposure to Potentially Toxic Elements in Household Dust: Spatial Distribution, Contamination Status, Positive Matrix Factorization, and Monte Carlo Simulation-Based Probabilistic Health Risk Assessment.","authors":"Mahmood Ahmed, Faryal Chaudhry, Anum Khaleeq, Arslan Usman, Zoya Sohail, Mahrukh Faisal, Khairia Mohammed Al-Ahmary, Muhammad Zubair, Masooma Irfan, Ali Abbas Aslam","doi":"10.1002/jat.70181","DOIUrl":"10.1002/jat.70181","url":null,"abstract":"<p><p>Indoor dust pollution is a serious environmental concern, especially when it carries potentially toxic elements (PTEs) that can harm human health. This study aimed to measure concentrations of PTEs (Cr, Mn, Ni, Co, Cu, Zn, Cd, and Pb) using ICP-OES in household dust collected from 30 residential sites in Lahore, Pakistan. This study combined positive matrix factorization (PMF) for source apportionment with Monte Carlo simulation to estimate the probabilistic human health risk. The concentration (mean ± SD) of analyzed PTEs found Zn (528.74 ± 180.75) at the highest concentration, followed by Mn (250.60 ± 17.18), Cu (50.32 ± 21.56), Pb (57.30 ± 15.98), Cr (59.52 ± 17.68), Ni (32.45 ± 6.72), Co (10.21 ± 2.84), and Cd (4.22 ± 2.78). Average daily dose (ADD), hazard quotient (HQ), hazard index (HI), and carcinogenic risk (CR) were also calculated to gauge potential impacts on human health. The contamination factor (CF) and geo-accumulation index (I<sub>geo</sub>) showed that household dust carried severe contamination overall, with the highest concern tied to Cd. HI values for all elements were less than 1, indicating no non-carcinogenic health risk for adults and children. The LCR value for Cr through various exposure pathways for children was determined to be 5.87 × 10<sup>-2</sup>, while the corresponding values for Ni were 1.09 × 10<sup>-2</sup> for children and 1.17 × 10<sup>-3</sup> for adults. This study indicates that improvements in management practices of indoor air quality will minimize harmful exposures. Children are a more sensitive population, and there is an urgent need for indoor exposure control policies.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4112-4131"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessment of Lurasidone Hydrochloride and Its Impurities for Neuronal and Cardiac Toxicities Using Integrated Toxicological Approaches.","authors":"Arya Patel, Nehangi Patel, Umang Shah, Archita Patel, Anjali Mahavar, Sahil Panjvani, Alkeshkumar Patel","doi":"10.1002/jat.70480","DOIUrl":"https://doi.org/10.1002/jat.70480","url":null,"abstract":"<p><p>Lurasidone hydrochloride (LH) has over 98 other impurities produced during its manufacturing and storage process. LH had two crucial impurities that were reported cytotoxic and genotoxic in nature: 4-chloro-1,2-benzisothiazole (Impurity 1) and 3-(1-piperazinyl)-1,2-benzisothiazole (Impurity 2). When the impurity threshold is exceeded due to chronic administration, evaluation of the toxicity of critical organs become crucial. A variety of endpoints were evaluated to assess the neurotoxicity of LH along with both impurities. The parameters related to neurotoxicity includes assessment of neurobehavioral abnormalities, evaluation of acetylcholinesterase and oxidative stress level by super oxide dismutase and malondialdehyde. Acetylcholinesterase is the most desirable targets affected by both impurities, according to AI-based toxicity prediction tools and docking scores. Cytotoxic nature of LH's and its impurities were discovered at 80-, 160-, and 320-μM concentrations through in vitro study with PC12 and H9C2 cell lines. In zebrafish study, at 0.2 μg/L of Impurity 2, there was an increase in mirror biting and time spent at the bottom of the tank, but there was no discernible decline in memory or learning during the T-maze assay. Impurity 1 and Impurity 2 demonstrated inhibition of AchE at the molecular level, which raises acetylcholine levels and causes excitotoxicity. Oxidative damage in neuronal cells is indicated by a lower amount of superoxide dismutase and a higher level of malondialdehyde. Cardiac histological damages like exhibiting myofilament fiber rupture and dissolution observed to decide toxicity induced damage. At 0.2-μg/L dose, the Impurity 2 has shown potential neurotoxicity as well cardiotoxicity in zebrafish study.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metal Accumulation, Liver Histopathology, and Human Health Risk Assessment Across Different Trophic Guilds in a Mining-Affected Neotropical River.","authors":"Breno Thuller, Alessandro Loureiro Paschoalini, Fabio Pereira Arantes, Cristiano Schetini de Azevedo, Elizete Rizzo, Nilo Bazzoli","doi":"10.1002/jat.70479","DOIUrl":"https://doi.org/10.1002/jat.70479","url":null,"abstract":"<p><p>Metal pollution in aquatic environments represents a recurring global concern; however, traditional paradigms often assume linear bioaccumulation patterns that may fail under catastrophic contamination scenarios. This study evaluated metal concentrations in water, sediment, and tissues of 10 fish species from different trophic guilds in the Paraopeba River after the Brumadinho dam collapse. Multivariate analyses (principal component analysis [PCA], generalized linear model [GLM], and PERMANOVA) were used to explore associations between metal concentrations, ecological traits, and body size integrated with liver histopathology (Histopathological Alteration Index) and Human Health Risk Assessment. Results revealed that metal concentrations in water and fish tissues exceeded regulatory limits, whereas sediment acted as the main reservoir of metals, exhibiting higher concentrations than water. High-severity liver damage was concentrated in benthic piscivores and benthopelagic detritivores, exposing a complex interplay between biomagnification and direct substrate contact. Human Health Risk Assessments indicated unacceptable noncarcinogenic risks driven by aluminum (Al), along with elevated carcinogenic risks for chromium (Cr) and cadmium (Cd) for both adults and children in the region analyzed. These findings demonstrate that ecological traits were associated with differences in metal accumulation, liver damage, and public health threats, reinforcing the need for nonlinear models in postdisaster regulatory frameworks.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxicological Assessment of Phthalate Plasticizers in Hydra vulgaris: Acute Toxicity, Genotoxicity, Developmental and Behavioural Effects.","authors":"Aditya Mohan Menon, Gayathri R Chandran, Ramaswamy Babu Rajendran, Kadalmani Balamuthu, Thirumurugan Ramasamy","doi":"10.1002/jat.70483","DOIUrl":"https://doi.org/10.1002/jat.70483","url":null,"abstract":"<p><p>Phthalates pose significant risks to aquatic ecosystems, though their effects on nontarget organisms have been reported, with little information on Hydra. This study evaluated the developmental, cytotoxic and behavioural toxicity of four phthalates, dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) at concentrations ranging between 1 and 100 mg/L in Hydra vulgaris over 96 h. DBP induced acute toxicity and lethality with a 48 h LC<sub>50</sub> of 5.3 mg/L. No mortality was observed for DEP, DMP and DEHP at this range of concentrations; however, DEP induced severe morphological changes and affected locomotion and tentacle movements of hydra at 100 mg/L. DBP caused distinct developmental effects, with disrupted regeneration and decreased reproductive output at the respective 1/10th and 1/2nd LC<sub>50</sub> concentrations of 0.53 and 2.7 mg/L. Behavioural endpoints such as foraging responses and locomotor activity were impaired at 0.53 mg/L. Furthermore, cytotoxicity, with 53% DNA damage and an increased rate of apoptosis, was observed. This study reveals that DBP was highly toxic to hydra compared to the other three phthalates. The order of toxicity was found to be DBP > DEP > DMP > DEHP.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fares Elghali, Kawther Bedchich, Nour Kacem, Mohamed Sami Aifa
{"title":"Cytotoxic and Oxidative Effects of Common Pesticides on Hepatic and Renal Cell Lines (HepG2 and Hek-293): Implications for Human Health and Environmental Safety.","authors":"Fares Elghali, Kawther Bedchich, Nour Kacem, Mohamed Sami Aifa","doi":"10.1002/jat.70485","DOIUrl":"https://doi.org/10.1002/jat.70485","url":null,"abstract":"<p><p>Modern agricultural practices expose humans and the environment to numerous chemical pesticides. Increasing evidence suggests that commercial pesticide formulations may exhibit toxicological properties that differ from those of their active ingredients alone due to the presence of co-formulants and additives. This study evaluated the cytotoxic and oxidative effects of commonly used commercial pesticide formulations in Tunisia on human hepatic (HepG2) and renal (HEK-293) cell lines. The tested formulations contained deltamethrin, permethrin, abamectin, imidacloprid, mancozeb, sulfur, alpha-chloralose, 2,4-D-2-ethylhexyl ester, florasulam, cloquintocet-mexyl, clodinafop-propargyl, and pinoxaden. Cell viability was assessed using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), and membrane damage was evaluated using the lactate dehydrogenase (LDH) assay. The half maximal inhibitory concentration (IC₅₀) values were determined for each formulation. Moncozeb exhibited the highest cytotoxicity in both cell lines, whereas sulfur and alpha-chloralose showed the lowest toxicity. Intracellular reactive oxygen species (ROS) measurements revealed significant oxidative stress following exposure to several formulations, which was associated with reduced cell viability and increased LDH release. Microscopic examination further demonstrated nuclear alterations consistent with apoptosis and necrosis in exposed cells. These findings highlight the importance of evaluating complete commercial pesticide formulations, rather than active ingredients alone, when assessing potential cytotoxic and oxidative effects. The results support the inclusion of formulation-based testing in toxicological risk assessment to better characterize potential human health hazards associated with pesticide exposure.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hemocyte, Biochemical, and Histopathological Responses of Biomphalaria alexandrina, the Egyptian Intermediate Host of Schistosoma mansoni, to Sublethal Deltamethrin Exposure.","authors":"Rasha Ezzat Mohamed Ali, Rasha Mohamed Gad El-Karim, Hassan El-Sayed Flefel, Mohamed Ramadan Habib","doi":"10.1002/jat.70477","DOIUrl":"https://doi.org/10.1002/jat.70477","url":null,"abstract":"<p><p>Deltamethrin is among the pyrethroids most frequently detected in Egyptian irrigation canals and drains, the same water bodies that support Biomphalaria alexandrina, the snail that transmits Schistosoma mansoni in Egypt. The objective of this study was to characterize the response of adult B. alexandrina to sublethal concentrations of a commercial deltamethrin formulation, using hemocyte, biochemical, and histopathological biomarkers. The hypothesis tested was that sublethal deltamethrin reduces the number of circulating hemocytes, alters the balance between hemocyte classes and damages hemocyte structure, at concentrations comparable with those measured in Egyptian watercourses. Adult snails were exposed to a commercial deltamethrin emulsifiable concentrate, the form applied in the field. The 24-h median lethal concentration (LC<sub>50</sub>) was 0.41 mg/L as nominal active ingredient. Snails were then held for 48 h or 10 d at nominal LC<sub>o</sub> (0.04 mg/L), LC<sub>5</sub> (0.25 mg/L), and LC<sub>10</sub> (0.28 mg/L), the lowest of these being 1.2-fold the highest deltamethrin concentration so far reported from Giza-area watercourses. Circulating hemocytes fell by 35% after 48 h and by 45% after 10 d at LC<sub>10</sub> (p < 0.001). The differential profile shifted toward granulocytes, from 66% in the 10-d control to 84% at LC<sub>10</sub> (p < 0.001), at the expense of hyalinocytes and blast-like cells. Exposed cells showed retracted pseudopodia, incomplete mitotic figures, cytoplasmic vacuolization, and membrane rupture. Binucleate hemocytes rose from 12.50% to 35.87% and micronucleated cells from 2.63% to 6.43% (p < 0.001). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glucose rose while total protein and albumin fell; reduced glutathione (GSH) rose alongside malondialdehyde (MDA) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>); and the digestive gland and the ovotestis degenerated with concentration. The hypothesis was accepted. The hemocyte compartment is a sensitive target of sublethal pyrethroid exposure in a snail of direct public health importance.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxicity of Organophosphate Insecticides and Biochemical Mechanisms Associated With Resistance in Field Populations of Plutella xylostella (L.) From Kashmir, India.","authors":"Bazila Rehman, Tariq Ahmad, Barkat Hussain","doi":"10.1002/jat.70464","DOIUrl":"https://doi.org/10.1002/jat.70464","url":null,"abstract":"<p><p>The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), is a globally important pest of cruciferous crops, for which intensive insecticide use has accelerated the evolution of resistance. However, the magnitude and biochemical basis of organophosphate resistance in P. xylostella populations from the Kashmir Valley remain poorly understood. Here, we quantified susceptibility to chlorpyrifos, dimethoate and quinalphos in nine field populations using leaf-dip bioassays and investigated associations between resistance phenotypes and activities of acetylcholinesterase (AChE), cytochrome P450 monooxygenases (CYP450) and glutathione S-transferases (GST). Resistance ratios (RR) varied substantially among populations, ranging from 8.48 to 34.67 for chlorpyrifos, 6.83-76.61 for dimethoate and 3.79-14.19 for quinalphos. Pulwama and Budgam consistently exhibited the highest resistance, whereas Ganderbal was the most susceptible population. Dimethoate resistance was particularly pronounced in Pulwama (RR = 76.61; LC<sub>50</sub> = 17.90 mL L<sup>-1</sup>). At the highest concentrations tested, corrected mortality remained below 50% across populations, although LC<sub>50</sub> estimates exceeding the tested concentration range should be interpreted cautiously. Enzyme assays revealed markedly elevated AChE and CYP450 activities in resistant populations, with increases of up to 34-fold and 10-fold, respectively, whereas GST activity showed no significant population-level difference. Spearman analysis further indicated significant positive associations of AChE, CYP450 and GST activities with quinalphos resistance (ρ = 0.79-0.91; p < 0.05), but not with chlorpyrifos or dimethoate resistance. These findings demonstrate substantial spatial heterogeneity in organophosphate susceptibility and indicate that biochemical resistance mechanisms are insecticide-specific rather than uniformly expressed across organophosphate resistance phenotypes. The pronounced dimethoate resistance, despite weak associations with the measured detoxification enzymes, suggests the involvement of additional mechanisms, including target-site insensitivity, alternative detoxification pathways, or reduced insecticide penetration. The results provide a baseline for resistance surveillance in Kashmir and support mechanism-informed insecticide rotation and resistance-management strategies for P. xylostella.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}